Elongation Factor ELL (Eleven-Nineteen Lysine-rich Leukemia) Acts as a Transcription Factor for Direct Thrombospondin-1 Regulation

The eleven-nineteen lysine-rich leukemia (ELL) gene undergoes translocation and fuses in-frame to the multiple lineage leukemia gene in a substantial proportion of patients suffering from acute forms of leukemia. Studies show that ELL indirectly modulates transcription by serving as a regulator for transcriptional elongation as well as for p53, U19/Eaf2, and steroid receptor activities. Our in vitro and in vivo data demonstrate that ELL could also serve as a transcriptional factor to directly induce transcription of the thrombospondin-1 (TSP-1) gene. Experiments using ELL deletion mutants established that full-length ELL is required for the TSP-1 up-regulation and that the trans-activation domain likely resides in the carboxyl terminus. Moreover, the DNA binding domain may localize to the first 45 amino acids of ELL. Not surprisingly, multiple lineage leukemia-ELL, which lacks these amino acids, did not induce expression from the TSP-1 promoter. In addition, the ELL core-response element appears to localize in the -1426 to -1418 region of the TSP-1 promoter. Finally, studies using zebrafish confirmed that ELL regulates TSP-1 mRNA expression in vivo, and ELL could inhibit zebrafish vasculogenesis, at least in part, through up-regulating TSP-1. Given the importance of TSP-1 as an anti-angiogenic protein, our findings may have important ramifications for better understanding cancer.

Caring for the Celtic cubs: Discursive constructions of mothers and mothering in the Irish childcare debate

Drawing on an understanding of the public sphere as a multiplicity of communicative and discursive spaces this paper examines the constructions of mothers, mothering and motherhood which emerged in recent debates about childcare in Ireland. Preliminary analysis of these discursive constructions suggest that they are often based on rhetoric, informed by stereotypical assumptions and rooted in frames of reference which mitigate against the emergence of alternative ways of understanding the issues of mothering and childcare. It will be argued that the reductionist and divisive nature of the childcare debate which ensued prior to the 2005 budget, stymied childcare policy development at a time when its unprecedented prominence on the political agenda and the strength of public finances could have underpinned a shift in policy approach. The paper concludes with an exploration of the ways in which feminist scholarship can challenge the Irish model of childcare policy, which continues to be premised on an understanding of childcare and the reconciliation of work and family life as the privatised responsibility of individual women.

Monstrative acts and becoming-monster: on identity, bodies, and the feminine other

Using two examples of literary monsters, the Creature in Mary Shelley’s Frankenstein (1818), and Grendel’s Mother in Beowulf, this thesis demonstrates the bearing fictional identities have on “real” bodies, through an examination of two further literary texts, David Henry Hwang’s play, M. Butterfly (1986) and J. M. Coetzee’s novel, Disgrace (1999). Western definitions of Being have historically divided body and mind, favouring the mind as formative of subjective experience and denigrating the body as secondary and impure. This thesis demonstrates that this mind/body binary is symptomatic of the masculine ontological imperative to disown the body and its effects on Being, simultaneously ridding itself of the feminine it believes is its irrational opposite. Using recent feminist reviews of the canon, which emphasise the body’s importance to ontology and demonstrate the conceptual association between the feminine and the corporeal, this thesis links performative identity practices to theories of monstrosity, explaining how fictional qualities adhere to monstrous bodies by proposing a new theoretical category, the “monstrative.” The monstrative is a performative force that makes the Other into a living sign of Otherness; however, unlike earlier theories of Othering, the monstrative accounts for the Other’s being other to herself. This thesis also attempts to read the misrepresented body of the Other as a possible site for more empowered identity performances, where the monstrous “I” is interpreted as a potentially positive model for identity practice, through the conceptualisation of identity as a process of Becoming rather than Being. The transferal from a noun to a verb not only emphasises the performativity of identity, but also suggests fluidity and multiplicity in identity practice, which always already indicates a monstrosity at work. Thus, while monstrative acts constitute bodies as monstrous, Becoming-monster is an empathetic response to the Other’s monstrosity.

La formation discursive eurorégionale. Articulation et approche sémantique d’un corpus multilingue

L’objectif de cet article est double :il s’agit, d’une part, de présenter un nouveau corpus permettant d’envisager le phénomène émergent de la communication transfrontalière en Europe et, d’autre part, de formuler trois questionnements utiles au cadrage de son analyse sémantique. À partir du corpus eurorégional – multilingue et multigenre - nous posons les questions de la dispersion des discours en ligne, de l’hétérogénéité des données et de la contextualisation de l’analyse. Notre démarche consiste à construire progressivement un modèle d’analyse adapté à l’appréhension, tantôt automatique et tantôt manuelle, de la diversité des textes. Enfin, nous proposons d’illustrer la démarche en l’appliquant à la mobilité, observable récurrent du corpus.

Technology on screen: projections, paranoia and discursive practice

This paper explores the extent to which film can be viewed as a discursive practice and as such the extent to which it can be seen as an element central to the essence of technology more universally defined. Our analysis of recurring visual and narrative motifs and metaphors around the representation of technology in specific films will consider how these representations are part of wider discursive practices around conceptualising technology.

The interleukin 1beta gene promoter polymorphism (-511) acts as a risk factor for psychosis in Alzheimer's dementia

The explanation for why some patients develop psychotic change in Alzheimer's disease (AD) is unclear. "Psychosis-modifier genes" may act in the setting of neurodegeneration to produce AD plus psychosis in a similar way to how genetic modulation during neurodevelopment leads to schizophrenia. Because there is increasing interest in the common disruption of cytokine pathways seen in both AD and schizophrenia, we tested the association between the functional interleukin-1beta -511 promoter polymorphism with delusions and hallucinations in AD. Significant associations between psychotic symptoms and the CC genotype (p = 0.001 - p = 0.043) and C allele (p = 0.014 vs p = 0.048) were found, thus confirming the previously noted increased risk in schizophrenia.

The discursive capacity of graphic design

The relationship between rhetoric and graphic design is presented in this article. The comparison between a classical orator and a graphic designer, between a discourse and a piece of design comes from the connections between with the communication and creativity. We will see how an application of the fundamentals of rhetoric can open new doors to the professional practice, the education of graphic design and the same theory of the rhetoric of the image.By the analysis of a design is exemplified the points of union that show how the arguments, operations, figures of discourse and rhetorical phases are present in the creative process of graphic design and how designers, perhaps unconsciously, use techniques that were traditional. In other words, graphic design is a rhetorical construction.There is then a transposition of a discourse model created by linguistic signs to a discourse model consists of visual and typographic signs, causing design is seen as a discursivediscipline that goes beyond the aesthetic component.

ATM acts downstream of ATR in the DNA damage response signaling of bystander cells.

This study identifies ataxia-telangiectasia mutated (ATM) as a further component of the complex signaling network of radiation-induced DNA damage in nontargeted bystander cells downstream of ataxia-telangiectasia and Rad3-related (ATR) and provides a rationale for molecular targeted modulation of these effects. In directly irradiated cells, ATR, ATM, and DNA-dependent protein kinase (DNA-PK) deficiency resulted in reduced cell survival as predicted by the known important role of these proteins in sensing DNA damage. A decrease in clonogenic survival was also observed in ATR/ATM/DNA-PK–proficient, nonirradiated bystander cells, but this effect was completely abrogated in ATR and ATM but not DNA-PK–deficient bystander cells. ATM activation in bystander cells was found to be dependent on ATR function. Furthermore, the induction and colocalization of ATR, 53BP1, ATM-S1981P, p21, and BRCA1 foci in nontargeted cells was shown, suggesting their involvement in bystander DNA damage signaling and providing additional potential targets for its modulation. 53BP1 bystander foci were induced in an ATR-dependent manner predominantly in S-phase cells, similar to ?H2AX foci induction. In conclusion, these results provide a rationale for the differential modulation of targeted and nontargeted effects of radiation.

Professing translation: the acts-in-between

Drawing on scholarship in translation ethics (Berman 1992; Cronin 2003) and performance studies (Conquergood 2002; Jackson 2004), this article approaches translation in the theatre from the double perspective of theory and practice. Professing translation as a model for the resolution of entrenched binaries (scholar/artist; theoretician/practitioner), the author sees the practice of translating for performance not just as a method of discovery or a hermeneutic tool but also as a mode of reflection that brings together both “readerly” and “writerly” approaches to text (Barthes 1974). By drawing on the experience of writing translations of García Lorca for the Belgrade Theatre, Calderón for the Royal Shakespeare Company, and Lope de Vega for the Watermill Theatre and the Washington Shakespeare Theatre, the article attempts to characterise such translation as an act of physical imagination, of a holistic understanding of both language and performance, into which textuality is incorporated and by which it is superseded. © John Benjamins Publishing Company