SdeK, a Histidine Kinase Required for Myxococcus xanthus Development

The sdeK gene is essential to the Myxococcus xanthus developmental process. We reported previously, based on sequence analysis (A. G. Garza, J. S. Pollack, B. Z. Harris, A. Lee, I. M. Keseler, E. F. Licking, and M. Singer, J. Bacteriol. 180:4628–4637, 1998), that SdeK appears to be a histidine kinase. In the present study, we have conducted both biochemical and genetic analyses to test the hypothesis that SdeK is a histidine kinase. An SdeK fusion protein containing an N-terminal polyhistidine tag (His-SdeK) displays the biochemical characteristics of a histidine kinase. Furthermore, histidine 286 of SdeK, the putative site of phosphorylation, is required for both in vitro and in vivo protein activity. The results of these assays have led us to conclude that SdeK is indeed a histidine kinase. The developmental phenotype of a ΔsdeK1 strain could not be rescued by codevelopment with wild-type cells, indicating that the defect is not due to the mutant's inability to produce an extracellular signal. Furthermore, the ΔsdeK1 mutant was found to produce both A- and C-signal, based on A-factor and codevelopment assays with a csgA mutant, respectively. The expression patterns of several Tn5lacZ transcriptional fusions were examined in the ΔsdeK1-null background, and we found that all C-signal-dependent fusions assayed also required SdeK for full expression. Our results indicate that SdeK is a histidine kinase that is part of a signal transduction pathway which, in concert with the C-signal transduction pathway, controls the activation of developmental-gene expression required to progress past the aggregation stage

Beyond Shakespeare's land of ire: Revisiting Ireland in English Renaissance drama

There has been much critical work on the symbolic centrality of Ireland to English Renaissance literature and drama. To focus on the latter, Shakespeare's histories have been read topically in terms of the contemporaneous Irish wars and also more historically, in terms of English colonialism in Ireland. Topical readings have been followed by allegorical approaches with, for instance, attention to Othello's “ghostly Irish subtext” (Hadfield, 1997) or Troilus and Cressida's memories of Elizabethan conflict in Ireland (Parker, 1996). Such interpretations suggest scholarly imaginativeness, the discovery of surprising meaning about a text we thought we knew, albeit within a Shakespeare‐centric frame. They further suggest the capacity of Ireland to enter a play's imaginary— as problem, as image, as other world. At stake here, then, are interrelated questions about what Ireland is doing in English Renaissance drama, where and when we expect to find it, and how we read it. This essay re‐examines the question of why and how Ireland features in plays by Shakespeare and other early modern dramatists. This deceptively simple question is intended to revisit some assumptions that underpin current critical understandings. Why Ireland features in plays has been largely understood as a function of historical contexts and processes: critics and scholars have turned to these as an important site of explanation, with the early modern colonialist discourse on Ireland given special prominence as a determinant of meaning. However, this focus has sidelined other considerations. This article argues for a broadening of context, beyond a focus on topical resonance, to allow for a consideration of dramatic genre and form, the imitative nature of dramatic writing, and the theatre companies themselves, as important factors that shaped how a text and context like Ireland and the Irish found its way into a play. This approach treats representations as a series of reciprocal markings, intertextual echoes, and foregrounds the capacity of a play to make meaning within its own frame. The objective here is less about discounting the political and ideological work of Renaissance plays than about exploring their possibilities to (re)imagine the early modern “land of ire.

Clinical standards for the management of adverse effects during treatment for TB

BACKGROUND: Adverse effects (AE) to TB treatment cause morbidity, mortality and treatment interruption. The aim of these clinical standards is to encourage best practise for the diagnosis and management of AE. METHODS: 65/81 invited experts participated in a Delphi process using a 5-point Likert scale to score draft standards. RESULTS: We identified eight clinical standards. Each person commencing treatment for TB should: Standard 1, be counselled regarding AE before and during treatment; Standard 2, be evaluated for factors that might increase AE risk with regular review to actively identify and manage these; Standard 3, when AE occur, carefully assessed and possible allergic or hypersensitiv-ity reactions considered; Standard 4, receive appropriate care to minimise morbidity and mortality associated with AE; Standard 5, be restarted on TB drugs after a serious AE according to a standardised protocol that includes active drug safety monitoring. In addition: Standard 6, healthcare workers should be trained on AE including how to counsel people undertaking TB treatment, as well as active AE monitoring and management; Standard 7, there should be active AE monitoring and reporting for all new TB drugs and regimens; and Standard 8, knowledge gaps identified from active AE monitoring should be systematically addressed through clinical research. CONCLUSION: These standards provide a person -centred, consensus-based approach to minimise the impact of AE TB treatment