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.

Declarative sensor knowledge in a robot monitoring system

Hardy, N. W., Barnes, D. P., Lee, M. (1987). Declarative sensor knowledge in a robot monitoring system. In: Languages for Sensor-Based Control in Robotics, Ulrich Rembold and Klaus H?rmann (eds), Springer-Verlag, p. 169-188.

Declarative Transport: No More Transport Protocols to Design, Only Policies to Specify

Transport protocols are an integral part of the inter-process communication (IPC) service used by application processes to communicate over the network infrastructure. With almost 30 years of research on transport, one would have hoped that we have a good handle on the problem. Unfortunately, that is not true. As the Internet continues to grow, new network technologies and new applications continue to emerge putting transport protocols in a never-ending flux as they are continuously adapted for these new environments. In this work, we propose a clean-slate transport architecture that renders all possible transport solutions as simply combinations of policies instantiated on a single common structure. We identify a minimal set of mechanisms that once instantiated with the appropriate policies allows any transport solution to be realized. Given our proposed architecture, we contend that there are no more transport protocols to design—only policies to specify. We implement our transport architecture in a declarative language, Network Datalog (NDlog), making the specification of different transport policies easy, compact, reusable, dynamically configurable and potentially verifiable. In NDlog, transport state is represented as database relations, state is updated/queried using database operations, and transport policies are specified using declarative rules. We identify limitations with NDlog that could potentially threaten the correctness of our specification. We propose several language extensions to NDlog that would significantly improve the programmability of transport policies.

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.

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.

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

Impure Thinking Practices and Clinical Acts: The Sonorous Becomings of Heidi Fast

This article introduces the recent sound works of Heidi Fast, a Finnish voice and performance artist. Fast’s creative practice operates between art and philosophy, and articulates several ‘zones of becoming’: what Fast designates as ‘the clinical’, ‘the virtual’ and ‘vocal thought-material’. Using a methodology of routing, the article shows how these zones emerge as aesthetic, ethical and political concerns within Fast’s work. Since 2005, Fast’s sound works have variously taken shape as miniature concerts, social sculptures, imaginary soundscapes and environmental music performances. Drawing upon the writings of theorists who have helped shape her practice, this article argues that Fast uses sound and voice to propose an ‘actualising philosophy’. This philosophy actualises virtualities (unrealised potentials), affecting transformative shifts through tiny mutations in perceptions and behaviours.

The lipopolysaccharide core of Brucella abortus acts as a shield against innate immunity recognition

Innate immunity recognizes bacterial molecules bearing pathogen-associated molecular patterns to launch inflammatory responses leading to the activation of adaptive immunity. However, the lipopolysaccharide (LPS) of the gram-negative bacterium Brucella lacks a marked pathogen-associated molecular pattern, and it has been postulated that this delays the development of immunity, creating a gap that is critical for the bacterium to reach the intracellular replicative niche. We found that a B. abortus mutant in the wadC gene displayed a disrupted LPS core while keeping both the LPS O-polysaccharide and lipid A. In mice, the wadC mutant induced proinflammatory responses and was attenuated. In addition, it was sensitive to killing by non-immune serum and bactericidal peptides and did not multiply in dendritic cells being targeted to lysosomal compartments. In contrast to wild type B. abortus, the wadC mutant induced dendritic cell maturation and secretion of pro-inflammatory cytokines. All these properties were reproduced by the wadC mutant purified LPS in a TLR4-dependent manner. Moreover, the core-mutated LPS displayed an increased binding to MD-2, the TLR4 co-receptor leading to subsequent increase in intracellular signaling. Here we show that Brucella escapes recognition in early stages of infection by expressing a shield against recognition by innate immunity in its LPS core and identify a novel virulence mechanism in intracellular pathogenic gram-negative bacteria. These results also encourage for an improvement in the generation of novel bacterial vaccines.