Mapping and understanding organizational change:Ireland 1922-2010

Capturing, mapping, and understanding organizational change within bureaucracies is inherently problematic, and the paucity of empirical research in this area reflects the traditional reluctance of scholars to pursue this endeavor. In this article, drawing on the Irish case of organizational change, potential avenues for overcoming such challenges are presented. Drawing on the resources of a time-series database that captures and codes the life cycle of all Irish public organizations since independence, the article explores the evolution of the Irish administrative system since the independence of the state in 1922. These findings provide some pointers toward overcoming the challenges associated with studying change in Whitehall-type bureaucracies. © Taylor & Francis Group, LLC.

Dissection of Host Cell Signal Transduction during Acinetobacter baumannii – Triggered Inflammatory Response

Infected airway epithelial cells up-regulate the expression of chemokines, chiefly IL-8, and antimicrobial molecules including ß-defensins (BD). Acinetobacter baumannii is a cause of hospital-acquired pneumonia. We examined whether A. baumannii induced the expressions of IL-8 and BD2 by airway epithelial cells and the receptors implicated in bacterial detection. A549 and human primary airway cells released IL-8 upon infection. A. baumannii-infected cells also increased the expression of BD2 which killed A. baummannii strains. IL-8 induction was via NF-B and mitogen-activated kinases p38 and p44/42-dependent pathways. A. baumannii engaged Toll-like receptor (TLR) 2 and TLR4 pathways and A549 cells could use soluble CD14 as TLRs co-receptor. A. baumannii lipopolysaccharide stimulated IL-8 release by A549 cells and sCD14 facilitated the recognition of the lipopolysaccharide. Mass spectrometry analysis revealed that A. baumannii lipid A structure matches those with endotoxic potential. These results demonstrate that airway epithelial cells produce mediators important for A. baumannii clearance. © 2010 March et al.

Lack of effect of glutamine administration to boost the innate immune system response in trauma patients in the intensive care unit

The use of glutamine as a dietary supplement is associated with a reduced risk of infection. We hypothesized that the underlying mechanism could be an increase in the expression and/or functionality of Toll-like receptors (TLR), key receptors sensing infections. The objective of this study was to evaluate whether glutamine supplementation alters the expression and functionality of TLR2 and TLR4 in circulating monocytes of trauma patients admitted to the intensive care unit (ICU).

Role of lipid A acylation in Yersinia enterocolitica virulence

Yersinia enterocolitica is an important human pathogen. Y. enterocolitica must adapt to the host environment, and temperature is an important cue regulating the expression of most Yersinia virulence factors. Here, we report that Y. enterocolitica 8081 serotype O:8 synthesized tetra-acylated lipid A at 37 degrees C but that hexa-acylated lipid A predominated at 21 degrees C. By mass spectrometry and genetic methods, we have shown that the Y. enterocolitica msbB, htrB, and lpxP homologues encode the acyltransferases responsible for the addition of C(12), C(14) and C(16:1), respectively, to lipid A. The expression levels of the acyltransferases were temperature regulated. Levels of expression of msbB and lpxP were higher at 21 degrees C than at 37 degrees C, whereas the level of expression of htrB was higher at 37 degrees C. At 21 degrees C, an lpxP mutant was the strain most susceptible to polymyxin B, whereas at 37 degrees C, an htrB mutant was the most susceptible. We present evidence that the lipid A acylation status affects the expression of Yersinia virulence factors. Thus, expression of flhDC, the flagellar master regulatory operon, was downregulated in msbB and lpxP mutants, with a concomitant decrease in motility. Expression of the phospholipase yplA was also downregulated in both mutants. inv expression was downregulated in msbB and htrB mutants, and consistent with this finding, invasion of HeLa cells was diminished. However, the expression of rovA, the positive regulator of inv, was not affected in the mutants. The levels of pYV-encoded virulence factors Yops and YadA in the acyltransferase mutants were not affected. Finally, we show that only the htrB mutant was attenuated in vivo.

Functional genomics to identify therapeutic prophylactic targets

Infectious diseases are a leading cause of global human mortality. The use of antimicrobials remains the most common strategy for treatment. However, the isolation of pathogens resistant to virtually all antimicrobials makes it urgent to develop effective therapeutics based on new targets. Here we review a new drug discovery paradigm focusing on identifying and targeting host factors important for infection as well as pathogen determinants involved in disease progression. We summarize innovative strategies which by combining bioinformatics with transcriptomics and chemical genetics have already identified host factors essential for pathogen entry, survival and replication. We describe how the discovery of RNA interference which allows loss-of-function studies has facilitated functional genomic studies in human cells. It is expected that these studies will identify targets to be used as host-directed drug therapy which, together with antimicrobials targeting microbial virulence factors, will efficiently eliminate the invading pathogen.

The Crowned Harp: Policing Northern Ireland (reprint 2006, 2010)

The Crowned Harp provides a detailed analysis of policing in Northern Ireland. Tracing its history from 1922, Ellison and Smyth portray the Royal Ulster Constabulary (RUC) as an organisation burdened by its past as a colonial police force. They analyse its perceived close relationship with unionism and why, for many nationalists, the RUC embodied the problem of the legitimacy of Northern Ireland, arguing that decisions made on the organisation, composition and ideology of policing in the early years of the state had consequences which went beyond the everyday practice of policing.

The authors provide an extended discussion of policing after the outbreak of civil unrest in 1969, ask why policing was cast in a paramilitary mould, and look at the use of special constabularies and the way in which the police dealt with social unrest which threatened to break down sectarian divisions. Examining the reorganisations of the RUC in the 1970s and 1980s, Ellison and Smyth focus on the various structural, legal and ideological components, the professionalisation of the force and the development of a coherent, if contradictory, ideology. The analysis of the RUC during this period sheds light on the problematic nature of using the police as a counter insurgency force in a divided society. Perceptions of the police, and the opinions of rank and file members are examined and an assessment is made of the various alternative models of policing, such as community policing and local control. This book offers important lessons about the nature of policing in divided societies.