The integration of lipid-sensing and anti-inflammatory effects: how the PPARs play a role in metabolic balance

The peroxisomal proliferating-activated receptors (PPARs) are lipid-sensing transcription factors that have a role in embryonic development, but are primarily known for modulating energy metabolism, lipid storage, and transport, as well as inflammation and wound healing. Currently, there is no consensus as to the overall combined function of PPARs and why they evolved. We hypothesize that the PPARs had to evolve to integrate lipid storage and burning with the ability to reduce oxidative stress, as energy storage is essential for survival and resistance to injury/infection, but the latter increases oxidative stress and may reduce median survival (functional longevity). In a sense, PPARs may be an evolutionary solution to something we call the 'hypoxia-lipid' conundrum, where the ability to store and burn fat is essential for survival, but is a 'double-edged sword', as fats are potentially highly toxic. Ways in which PPARs may reduce oxidative stress involve modulation of mitochondrial uncoupling protein (UCP) expression (thus reducing reactive oxygen species, ROS), optimising forkhead box class O factor (FOXO) activity (by improving whole body insulin sensitivity) and suppressing NFkB (at the transcriptional level). In light of this, we therefore postulate that inflammation-induced PPAR downregulation engenders many of the signs and symptoms of the metabolic syndrome, which shares many features with the acute phase response (APR) and is the opposite of the phenotype associated with calorie restriction and high FOXO activity. In genetically susceptible individuals (displaying the naturally mildly insulin resistant 'thrifty genotype'), suboptimal PPAR activity may follow an exaggerated but natural adipose tissue-related inflammatory signal induced by excessive calories and reduced physical activity, which normally couples energy storage with the ability to mount an immune response. This is further worsened when pancreatic decompensation occurs, resulting in gluco-oxidative stress and lipotoxicity, increased inflammatory insulin resistance and oxidative stress. Reactivating PPARs may restore a metabolic balance and help to adapt the phenotype to a modern lifestyle.

Corticospinal tract integrity and lesion volume play different roles in chronic hemiparesis and its improvement through motor practice

Background. Initial evidence suggests that the integrity of the ipsilesional corticospinal tract (CST) after stroke is strongly related to motor function in the chronic state but not the treatment gain induced by motor rehabilitation. Objective. We examined the association of motor status and treatment benefit by testing patients with a wide range of severity of hemiparesis of the left and right upper extremity. Method. Diffusion tensor imaging was performed in 22 patients beyond 12 months after onset of stroke with severe to moderate hemiparesis. Motor function was tested before and after 2 weeks of modified constraint-induced movement therapy. Results. CST integrity, but not lesion volume, correlated with the motor ability measures of the Wolf Motor Function Test and the Motor Activity Log. No differences were found between left and right hemiparesis. Motor performance improved significantly with the treatment regime, and did so equally for patients with left and right arm paresis. However, treatment benefit was not associated with either CST integrity or lesion volume. Conclusion. CST integrity correlated best in this small trial with chronic long-term status but not treatment-induced improvements. The CST may play a different role in the mechanisms mediating long-term outcome compared to those underlying practice-induced gains after a chronic plateau in motor function.

Digital code-switching between Cypriot and Standard Greek: performance and identity play online

Studies of code-switching in writing are very limited in comparison with the numerous investigations of this phenomenon in oral communication. Recent research has revealed that in text-based computer-mediated communication internet users bring into play the various languages available in their linguistic repertoire and, consequently, switch between them. In this case study, I investigate digital code-switching between Cypriot and Standard Greek, the two varieties of Greek spoken on the island of Cyprus. Following Auer’s conversation analytic approach and Gafaranga’s view that conversational structure coexists with social structure, I investigate code-switching in online interactions. The data to be analysed here, unlike those considered in most studies of code-switching, are written data, obtained from channel #Cyprus of Internet Relay Chat. The results suggest that code-switching in writing is influenced not only by macro-sociolinguistic factors, but they are also shaped by the medium- and social-specific characteristics of Internet Relay Chat. This, in turn, allows internet users to gain access to different roles and perform various identities within this online context.

“There’s something very familiar about all this”: generic play and performance in the Back to the Future trilogy (Robert Zemeckis, 1985, 1989, 1990)

The Back to the Future Trilogy incorporates several different generic elements, including aspects of the fifties teen movie, science fiction, comedy and the western. These different modes playfully intertwine with each other creating a complex world of repetitions, echoes and modulations. This essay seeks to interrogate the construction of generic elements and the play between them through a close analysis of a repeated performance. Genre is signalled through various strategies employed within the construction of mise-en-scène, a significant portion of this, as I would like to argue, is transmitted through performance. The material detail of a performance – incorporating gesture, movement, voice, and even surrounding elements such as costume – as well as the way it its presented within a film is key to the establishment, invocation and coherence of genre. Furthermore, attention to the complexity of performance details, particularly in the manner in which they reverberate across texts, demonstrates the intricacy of genre and its inherent mutability. The Back to the Future trilogy represents a specific interest in the flexibility of genre. Within each film, and especially across all three, aspects of various genres are interlaced through both visual and narrative detail, thus constructing a dense layer of references both within and without the texts. To explore this patterning in more detail I will interrogate the contribution of performance to generic play through close analysis of Thomas F. Wilson’s performance of Biff/Griff/Burford Tannen and his central encounter with Marty McFly (Michael J. Fox) in each film. These moments take place in a fifties diner, a 1980s retro diner and a saloon respectively, each space contributing the similarities and differences in each repetition. Close attention to Wilson’s performance of each related character, which contains both modulations and repetitions used specifically to place each film’s central generic theme, demonstrates how embedded the play between genres and their flexibility is within the trilogy.

The spaces of the Wednesday Play (BBC TV 1964–1970): production, technology and style

The BBC television drama anthology The Wednesday Play, broadcast from 1964-70 on the BBC1 channel, was high-profile and often controversial in its time and has since been central to accounts of British television’s ‘golden age’. This article demonstrates that production technologies and methods were more diverse at that time than is now acknowledged, and that The Wednesday Play dramas drew both approving but also very critical responses from contemporary viewers and professional reviewers. This article analyses the ways that the physical spaces of production for different dramas in the series, and the different technologies of shooting and recording that were adopted in these production spaces, are associated with but do not determine aesthetic style. The adoption of single-camera location filming rather than the established production method of multi-camera studio videotaping in some of the dramas in the series has been important to The Wednesday Play’s significance, but each production method was used in different ways. The dramas drew their dramatic forms and aesthetic emphases from both theatre and cinema, as well as connecting with debates about the nature of drama for television. Institutional and regulatory frameworks such as control over staff working away from base, budgetary considerations and union agreements also impacted on decisions about how programmes were made. The article makes use of records from the BBC Written Archives Centre, as well as published scholarship. By placing The Wednesday Play in a range of overlapping historical contexts, its identity can be understood as transitional, differentiated and contested.

Collabowrighting the hyper(play)text: a postdramatic digital poetics

The aim of this research is to exhibit how literary playtexts can evoke multisensory trends prevalent in 21st century theatre. In order to do so, it explores a range of practical forms and theoretical contexts for creating participatory, site-specific and immersive theatre. With reference to literary theory, specifically to semiotics, reader-response theory, postmodernism and deconstruction, it attempts to revise dramatic theory established by Aristotle’s Poetics. Considering Gertrude Stein’s essay, Plays (1935), and relevant trends in theatre and performance, shaped by space, technology and the everchanging role of the audience member, a postdramatic poetics emerges from which to analyze the plays of Mac Wellman and Suzan-Lori Parks. Distinguishing the two textual lives of a play as the performance playtext and the literary playtext, it examines the conventions of the printed literary playtext, with reference to models of practice that radicalize the play form, including works by Mabou Mines, The Living Theatre and Fiona Templeton. The arguments of this practice-led Ph.D. developed out of direct engagement with the practice project, which explores the multisensory potential of written language when combined with hypermedia. The written thesis traces the development process of a new play, Rumi High, which is presented digitally as a ‘hyper(play)text,’ accessible through the Internet at www.RumiHigh.org. Here, ‘playwrighting’ practice is expanded spatially, collaboratively and textually. Plays are built, designed and crafted with many layers of meaning that explore both linguistic and graphic modes of poetic expression. The hyper(play)text of Rumi High establishes playwrighting practice as curatorial, where performance and literary playtexts are in a reciprocal relationship. This thesis argues that digital writing and reading spaces enable new approaches to expressing the many languages of performance, while expanding the collaborative network that produces the work. It questions how participatory forms of immersive and site-specific theatre can be presented as interactive literary playtexts, which enable the reader to have a multisensory experience. Through a reflection on process and an evaluation of the practice project, this thesis problematizes notions of authorship and text.

CPDs and 6-4PPs play different roles in UV-induced cell death in normal and NER-deficient human cells

Ultraviolet (UV) light generates two major DNA lesions: cyclobutane pyrimidine dimers (CPDs) and pyrimidine-(6-4)-pyrimidone photoproducts (6-4PPs), but the specific participation of these two lesions in the deleterious effects of UV is a longstanding question. In order to discriminate the precise role of unrepaired CPDs and 6-4PPs in UV-induced responses triggering cell death, human fibroblasts were transduced by recombinant adenoviruses carrying the CPD-photolyase or 6-4PP-photolyase cDNAs. Both photolyases were able to prevent UV-induced apoptosis in cells deficient for nucleotide excision repair (NER) to a similar extent, while in NER-proficient cells UV-induced apoptosis was prevented only by CPD-photolyase, with no effects observed when 6-4PPs were removed by the specific photolyase. These results strongly suggest that both CPDs and 6-4PPs contribute to UV-induced apoptosis in NER-deficient cells, while in NER-proficient cells, CPDs are the only lesions responsible for UV-killing, probably due to the rapid repair of 6-4PPs by NER. As a consequence, the difference in skin photosensitivity, including carcinogenesis, of most of the xeroderma pigmentosum patients and of normal people is probably not only a quantitative aspect, but depends on the type of DNA damage induced by sunlight and its rate of repair. (c) 2007 Elsevier B.V. All rights reserved.

Donor bone marrow cells play a role in the prevention of accelerated graft rejection induced by semi-allogeneic spleen cells in transplantation

Spleen or spleen plus bone marrow cells from (BALB/c x C57Bl/6)F1 donors were transferred into BALB/c recipients 21 days before skin or cardiac transplantation. Prolonged graft survival was observed on recipients treated with the mixture of donor-derived cells as compared to those treated with spleen cells alone. We evaluated the expression of CD45RB and CD44 by splenic CD4(+) and CD8(+) T cells 7 and 21 days after donor cell transfer. The populations of CD8(+)CD45RB(low) and CD8(+)CD44(high) cells were significantly decreased in mice pre-treated with donor spleen and bone marrow cells as compared to animals treated with spleen cells only, although these cells expanded in both groups when compared to an earlier time-point. No differences were observed regarding CD4+ T cell population when recipients of donor-derived cells were compared. An enhanced production of IL-10 was observed seven days after transplantation in the supernatants of spleen cell cultures of mice treated with spleen and bone marrow cells. Taken together these data suggest that donor-derived bone marrow cells modulate the sensitization of the recipient by semi-allogeneic spleen cells in part by delaying the generation of activated/memory CD8(+) T cells leading to enhanced graft survival. (c) 2007 Elsevier B.V. All rights reserved.

Verdi's Settings of Shakespeare : from Play to Liberetto to Opera

As a Senior Scholar pursuing the topic, Verdi's Settings of Shakespeare: From Play to Libretto to Opera, I have endeavoured to study a project relevant to my majors, Music and English. During first semester, I carefully analysed Shakespeare's plays, Macbeth, Othello and Falstaff. The highlight of my project was in January when I travelled to New York City and spent the day working with the Metropolitan Opera Guild. I was also able to see a performance of Verdi's Othello with Jon Vickers in the lead role. During the second semester, I studied the musical aspects of the compositions. I spent time analysing musical passages and relating them to the plays and the operas. I was also able to continue my study of Italian, which I find extremely beneficial while studying Verdi's libretti. On Monday, 13th May, 1974, I gave a lecture presentation of my project. At this time, I showed slides of Metropolitan productions of the operas, presented my own rendition of five arias (in costume) and talked about comparisions between the plays and the operas. I applied for a Rotary Fellowship to take my project to Europe and am presently waiting to hear the results. If I do receive the fellowship, I am planning to spend a year studying the plays and operas in England and Italy. Afterwards, I hope to publish a paper explaining my findings. The paper is divided into six sections. The first section is an introduction which explains the period of Romanticism and its relationship to Shakespeare and Verdi. The second section is devoted to discussing the librettist for Macbeth, Francesco Piave. Following this section the opera Macbeth is discussed. Arrigo Boito, the librettist for Otello and Falstaff is discussed in the fourth section. The last two sections deal with Otello and Falstaff. I have also included a number of musical selections to better explain certain passages. My project has been invaluable to me. My Senior Scholar project has allowed me the freedom of independent study as well as a means of tying my majors together.

Gravity: a new play by Greg Belanger

Gravity was first performed at Strider Theatre, Colby College in Waterville, Maine. It was directed by the author with the following cast: STEVEN: Harold Withee PAMELA: Sue Larsen JEREMY: Jason Reifler IXXTOR: Amanda Starr MOTHER: Catherine C. Coyne BREIT: Scott W. Cole TONI: Laura Smishkiss