Suicide plays

Suicide is a uniquely human behaviour and has always elicited strong - usually negative - opinions. Thus I would like to state from the very outset that this morbid collection of writing (all separately published elsewhere previously) should not be seen as an attempt to glamorise the act of felo-de-se. Nevertheless, one needs to recognise the inherent theatricality of suicide: too often it is a petulant, peevish performance intended to convey a bitter message to the audience of those left behind. Unfortunately, it is also a performance that many similarly unhappy souls try to emulate, and this phenomenon, known as “The Werther Effect”, is the subject of the first paper, which serves as a most appropriate introduction to the four plays that follow it. The first play, entitled “Hamlet + Ophelia = ?”, is deliberately provocative, and may easily be misunderstood as a call to commit self-murder. It is hoped, however, that the protagonists of this angry little piece are seen to be impetuous and childish, rather than noble or deep. The second play, “Games for Married Couples”, is less about seppuku than it is about the despair of child-less marriage. It is not much happier than the first, but may nevertheless raise a smile or two. “His ... or Her ... Suicide”, on the other hand, is utterly frivolous. I am sure no reader will take it seriously. Finally, and circuitously, is the stage adaptation (and translation) of Goethe’s classic 1774 novella "Die Leiden des jungen Werthers". This piece was produced as part of my 2005 Master of Creative Arts at the University of Melbourne in Australia. Many thanks must go to my supervisor, Associate Professor Angela O’Brien, for prodding and poking me until the thesis was of an acceptable standard.

Independent Brisbane: Four Plays [BOOK REVIEW]

Independent Brisbane: Four Plays is, as the title suggests, a collection of plays by independent theatre-makers and theatre-making collectives in Brisbane in the 2002– 07 period, including Marcel Dorney’s Harriers (6–51), the nest’s The Knowing of Mary Poppins (52–102), Linda Hassall’s Post Office Rose (103–71) and Maxine Mellor’s Magda’s Fascination with Wax Cats (172–216). According to the contextualising information on the book’s back cover, these plays are ‘distinctive’ in content, story and style, ‘[y]et carry with them what is characteristic of the city they come from – a preoccupation with landscape, creation in tightly knit collaborative teams and brave, often unexpected, theatrical choices’.

The 48 hour game making challenge: Jams, Jellybeans and the fruits of passion

Performance / Event Documentation and Curatorial Research Statement

GCAP 2010 presentation : jams, jellybeans and the fruits of passion

In 2010 we realised that our fifth 48 hour game making competition was more than a mere event but that we were actually watching our local games industry enact a very intense process of community making and reflective practice. This presentation of our early research on the event was an invited spectacle at the Games Connect Australia Pacific Conference 2010 held at the Gold Coast Convention Centre, 14-15 October 2010. Abstract: Jams, Jellybeans and the fruit of passion: if games are about creating innovative player experience, then the place to start is how we set up game design education as an experience Authors: truna aka j.turner – Brisbane IGDA & Lubi Thomas, Mt Nebo Studios The 48 hour game making challenge has grown since it started in 2007 to accommodate 20 teams, some of the teams are professionals, some are made of people who are working in other industries, most are made of students from the various tertiary institutes around town. We still don’t quite understand why these mad people sign up for 48 hours of intense creativity just for the jelly beans we hand out as prizes but we do suspect that the space we give them and the passion they bring to the event offers those of us involved in the education side of the games industry really vital insights into what is critical and important in terms of education. The Australian games industry really needs these people, they are bright and ingenious and they make the most amazing games. But you won't get them by telling tertiary institutions what you fancy this year in terms of skills and criteria; you will get them by fostering their creativity and passion. If games are about creating innovative player experience, then the place to start is how we set up game design education as an experience.

Jams, jelly beans and the fruits of passion - art book (26 Pages)

Statement: Jams, Jelly Beans and the Fruits of Passion Let us search, instead, for an epistemology of practice implicit in the artistic, intuitive processes which some practitioners do bring to situations of uncertainty, instability, uniqueness, and value conflict. (Schön 1983, p40) Game On was born out of the idea of creative community; finding, networking, supporting and inspiring the people behind the face of an industry, those in the mist of the machine and those intending to join. We understood this moment to be a pivotal opportunity to nurture a new emerging form of game making, in an era of change, where the old industry models were proving to be unsustainable. As soon as we started putting people into a room under pressure, to make something in 48hrs, a whole pile of evolutionary creative responses emerged. People refashioned their craft in a moment of intense creativity that demanded different ways of working, an adaptive approach to the craft of making games – small – fast – indie. An event like the 48hrs forces participants’ attention onto the process as much as the outcome. As one game industry professional taking part in a challenge for the first time observed: there are three paths in the genesis from idea to finished work: the path that focuses on mechanics; the path that focuses on team structure and roles, and the path that focuses on the idea, the spirit – and the more successful teams put the spirit of the work first and foremost. The spirit drives the adaptation, it becomes improvisation. As Schön says: “Improvisation consists on varying, combining and recombining a set of figures within the schema which bounds and gives coherence to the performance.” (1983, p55). This improvisational approach is all about those making the games: the people and the principles of their creative process. This documentation evidences the intensity of their passion, determination and the shit that they are prepared to put themselves through to achieve their goal – to win a cup full of jellybeans and make a working game in 48hrs. 48hr is a project where, on all levels, analogue meets digital. This concept was further explored through the documentation process. All of these pictures were taken with a 1945 Leica III camera. The use of this classic, film-based camera, gives the images a granularity and depth, this older slower technology exposes the very human moments of digital creativity. ____________________________ Schön, D. A. 1983, The Reflective Practitioner: How Professionals Think in Action, Basic Books, New York

Spin

“Spin” borrows idioms and metaphors from sports commentary and squeezes them into a single emotional rollercoaster. Accompanied by a driving soundtrack, text appears and disappears one word at a time. As the work progresses, multiple words fade in and out at the same time, filling the screen and testing our ability to read and assimilate these well-worn phrases. On the one hand, the work mimes some of what we enjoy about sport – its ability to take us to another place, to incite passion and emotion, and to enable us to share in common experiences, goals and desires. On the other hand, it plays up the hyperbolic language often associated with sports broadcasting. The very language that helps take us to another place, incite passion and make us feel part of something bigger than ourselves, is pushed to its extreme and starts to burst at the seams. This work was commissioned for “Kick Off: contemporary video art program” at Metricon Stadium, Gold Coast, and supported by Project Services, Department of Public Works, Queensland Government.

Delta opioid-receptor function in the dorsal striatum plays a role in high levels of ethanol consumption in rats

Binge-like patterns of excessive drinking during young adulthood increase the propensity for alcohol use disorders (AUDs) later in adult life; however, the mechanisms that drive this are not completely understood. Previous studies showed that the δ-opioid peptide receptor (DOP-R) is dynamically regulated by exposure to ethanol and that the DOP-R plays a role in ethanol-mediated behaviors. The aim of this study was to determine the role of the DOP-R in high ethanol consumption from young adulthood through to late adulthood by measuring DOP-R-mediated [(35)S]GTPγS binding in brain membranes and DOP-R-mediated analgesia using a rat model of high ethanol consumption in Long Evans rats. We show that DOP-R activity in the dorsal striatum and DOP-R-mediated analgesia changes during development, being highest during early adulthood and reduced in late adulthood. Intermittent access to ethanol but not continuous ethanol or water from young adulthood leads to an increase in DOP-R activity in the dorsal striatum and DOP-R-mediated analgesia into late adulthood. Multiple microinfusions of naltrindole into the dorsal striatum or multiple systemic administration of naltrindole reduces ethanol consumption, and following termination of treatment, DOP-R activity in the dorsal striatum is attenuated. These findings suggest that DOP-R activity in the dorsal striatum plays a role in high levels of ethanol consumption and suggest that targeting the DOP-R is an alternative strategy for the treatment of AUDs.

The α5 neuronal nicotinic acetylcholine receptor subunits plays an important role in the sedative effects of ethanol but does not modulate consumption in mice

Alcohol use disorders (AUDs) are a major public health problem, and the few treatment options available to those seeking treatment offer only modest success rates. There remains a need to identify novel targets for the treatment of AUDs. The neuronal nicotinic acetylcholine receptors (nAChRs) represent a potential therapeutic target in the brain, as recent human genetic studies have implicated gene variants in the α5 nAChR subunit as high risk factors for developing alcohol dependence. Here, we evaluate the role of 5* nAChR for ethanol-mediated behaviors using α5+/+ and α5-/- mice. We characterized the effect of hypnotic doses of ethanol and investigated drinking behavior using an adapted Drinking-in-the Dark (DID) paradigm that has been shown to induce high ethanol consumption in mice. We found the α5 subunit to be critical in mediating the sedative effects of ethanol. The α5-/- mice showed slower recovery from ethanol-induced sleep, as measured by loss of righting reflex. Additionally the α5-/- mice showed enhanced impairment to ethanol-induced ataxia. We found the initial sensitivity to ethanol and ethanol metabolism to be similar in both α5+/+ and α5-/- mice. Hence the enhanced sedation is likely due to a difference in the acute tolerance of ethanol in mice deficient of the α5 subunit. However the α5 subunit did not play a role in ethanol consumption for ethanol concentrations ranging from 5% to 30% in the DID paradigm. Additionally, varenicline (Chantix®) was effective in reducing ethanol intake in α5-/- mice. Together, our data suggest that the α5 nAChR subunit is important for the sedative hypnotic doses of ethanol but does not play a role in ethanol consumption. Varenicline can be a treatment option even when there is loss of function of the α5 nAChR subunit.

Exo1 plays a major role in DNA end resection in humans and influences double-strand break repair and damage signaling decisions

The resection of DNA double-strand breaks (DSBs) to generate ssDNA tails is a pivotal event in the cellular response to these breaks. In the two-step model of resection, primarily elucidated in yeast, initial resection by Mre11-CtIP is followed by extensive resection by two distinct pathways involving Exo1 or BLM/WRN-Dna2. However, resection pathways and their exact contributions in humans in vivo are not as clearly worked out as in yeast. Here, we examined the contribution of Exo1 to DNA end resection in humans in vivo in response to ionizing radiation (IR) and its relationship with other resection pathways (Mre11-CtIP or BLM/WRN). We find that Exo1 plays a predominant role in resection in human cells along with an alternate pathway dependent on WRN. While Mre11 and CtIP stimulate resection in human cells, they are not absolutely required for this process and Exo1 can function in resection even in the absence of Mre11-CtIP. Interestingly, the recruitment of Exo1 to DNA breaks appears to be inhibited by the NHEJ protein Ku80, and the higher level of resection that occurs upon siRNA-mediated depletion of Ku80 is dependent on Exo1. In addition, Exo1 may be regulated by 53BP1 and Brca1, and the restoration of resection in BRCA1-deficient cells upon depletion of 53BP1 is dependent on Exo1. Finally, we find that Exo1-mediated resection facilitates a transition from ATM- to ATR-mediated cell cycle checkpoint signaling. Our results identify Exo1 as a key mediator of DNA end resection and DSB repair and damage signaling decisions in human cells.

The human topoisomerase I damage response plays a role in apoptosis

Previous studies have shown that human topoisomerase I cleavage complexes form as a response to various DNA damages in vivo, the so called human topoisomerase I “damage response”. It was suggested that this damage response may play a role in DNA repair as well as in apoptosis, but only very few investigations have been done and the significance of the damage response still remains unclear. Here we demonstrate that human topoisomerase I cleavage complexes induced by high doses of UV irradiation are highly stable for up to 48 h. Furthermore, we show that human topoisomerase I cleavage complexes correlate with apoptosis. However, at low UV doses the cleavage complex level was very low and the complexes were repaired. Surprisingly, we found that high levels of stable cleavage complexes were not only found in UV-irradiated cells but also in untreated cells that underwent apoptosis. A possible role of human topoisomerase I in apoptosis is discussed.

Calcitonin receptor plays a physiological role to protect against hypercalcemia in mice

It is well established that calcitonin is a potent inhibitor of bone resorption; however, a physiological role for calcitonin acting through its cognate receptor, the calcitonin receptor (CTR), has not been identified. Data from previous genetically modified animal models have recognized a possible role for calcitonin and the CTR in controlling bone formation; however, interpretation of these data are complicated, in part because of their mixed genetic background. Therefore, to elucidate the physiological role of the CTR in calcium and bone metabolism, we generated a viable global CTR knockout (KO) mouse model using the Cre/loxP system, in which the CTR is globally deleted by >94% but <100%. Global CTRKOs displayed normal serum ultrafiltrable calcium levels and a mild increase in bone formation in males, showing that the CTR plays a modest physiological role in the regulation of bone and calcium homeostasis in the basal state in mice. Furthermore, the peak in serum total calcium after calcitriol [1,25(OH)2D3]-induced hypercalcemia was substantially greater in global CTRKOs compared with controls. These data provide strong evidence for a biological role of the CTR in regulating calcium homeostasis in states of calcium stress.

The kiwifruit lycopene beta-cyclase plays a significant role in carotenoid accumulation in fruit

The composition of carotenoids, along with anthocyanins and chlorophyll, accounts for the distinctive range of colour found in the Actinidia (kiwifruit) species. Lutein and beta-carotene are the most abundant carotenoids found during fruit development, with beta-carotene concentration increasing rapidly during fruit maturation and ripening. In addition, the accumulation of beta-carotene and lutein is influenced by the temperature at which harvested fruit are stored. Expression analysis of carotenoid biosynthetic genes among different genotypes and fruit developmental stages identified Actinidia lycopene beta-cyclase (LCY-β) as the gene whose expression pattern appeared to be associated with both total carotenoid and beta-carotene accumulation. Phytoene desaturase (PDS) expression was the least variable among the different genotypes, while zeta carotene desaturase (ZDS), beta-carotene hydroxylase (CRH-β), and epsilon carotene hydroxylase (CRH-ε) showed some variation in gene expression. The LCY-β gene was functionally tested in bacteria and shown to convert lycopene and delta-carotene to beta-carotene and alpha-carotene respectively. This indicates that the accumulation of beta-carotene, the major carotenoid in these kiwifruit species, appears to be controlled by the level of expression of LCY-β gene.

Senataxin plays an essential role with DNA damage response proteins in meiotic recombination and gene silencing

Senataxin, mutated in the human genetic disorder ataxia with oculomotor apraxia type 2 (AOA2), plays an important role in maintaining genome integrity by coordination of transcription, DNA replication, and the DNA damage response. We demonstrate that senataxin is essential for spermatogenesis and that it functions at two stages in meiosis during crossing-over in homologous recombination and in meiotic sex chromosome inactivation (MSCI). Disruption of the Setx gene caused persistence of DNA double-strand breaks, a defect in disassembly of Rad51 filaments, accumulation of DNA:RNA hybrids (R-loops), and ultimately a failure of crossing-over. Senataxin localised to the XY body in a Brca1-dependent manner, and in its absence there was incomplete localisation of DNA damage response proteins to the XY chromosomes and ATR was retained on the axial elements of these chromosomes, failing to diffuse out into chromatin. Furthermore persistence of RNA polymerase II activity, altered ubH2A distribution, and abnormal XY-linked gene expression in Setx⁻/⁻ revealed an essential role for senataxin in MSCI. These data support key roles for senataxin in coordinating meiotic crossing-over with transcription and in gene silencing to protect the integrity of the genome.