Eye Spy Private High: Re-conceptualizing High Policing Theory

This paper contests traditional analyses of high policing, suggesting that it needs to be decoupled (in theoretical terms) from its umbilical linkage to public actors and the preservation and augmentation of state authority. Arguing that conventional conceptualizations of high policing fail to acknowledge the role of private actors, we adopt the term `private high policing' to more accurately reflect the complexity of this paradigm. In particular, we note a long legacy of protecting dominant interests within corporate power structures, as well as increased involvement in outsourced security services for Western states. This has reached its zenith in the recent conflict/reconstruction efforts in Iraq. Eschewing conventional notions of the `proxy' debate, we propose a more complex relationship of obfuscation whereby both public and private high policing actors cross-permeate and coalesce in the pursuit of symbiotic state and corporate objectives.

Role of p190RhoGAP in beta2 Integrin Regulation of RhoA in Human Neutrophils

We found that engagement of beta 2 integrins on human neutrophils induced activation of RhoA, as indicated by the increased ratio of GTP:GTP 1 GDP recovered on RhoA and translocation of RhoA to a membrane fraction. The clustering of beta 2 integrins also induced a time-dependent increase in GDP bound to RhoA, which correlated with beta 2 integrin-induced activation of p190RhoGAP. The activation of p190RhoGAP was completely blocked by [4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine] (PP1), a selective inhibitor of Src family tyrosine kinases. However, clustering of beta 2 integrins did not increase the basal tyrosine phosphorylation of p190RhoGAP, nor did it affect the amount of p120RasGAP bound to p190RhoGAP. Instead, the beta 2 integrin-induced activation of p190RhoGAP was accompanied by increased tyrosine phosphorylation of a p190RhoGAP-associated protein, p120RasGAP, and accumulation of both p120RasGAP and p190RhoGAP in a membrane fraction. PP1 blocked the beta 2 integrin-induced phosphorylation of p120RasGAP, as well as the translocation of p190RhoGAP and p120RasGAP, but it did not affect the accumulation of RhoA in the membrane fraction. In agreement with the mentioned findings, PP1 also increased the GTP:GTP 1 GDP ratio recovered on RhoA immunoprecipitated from beta2 integrin-stimulated cells. Thus, in neutrophils, beta 2 integrin-induced activation of p190RhoGAP requires a signal from a Src family tyrosine kinase, but it does not occur via the signaling pathway responsible for activation of RhoA.

Down-regulation of Rac Activity during beta 2 Integrin-mediated Adhesion of Human Neutrophils

In human neutrophils, beta2 integrin engagement mediated a decrease in GTP-bound Rac1 and Rac2. Pretreatment of neutrophils with LY294002 or PP1 (inhibiting phosphatidylinositol 3-kinase (PI 3-kinase) and Src kinases, respectively) partly reversed the beta2 integrin-induced down-regulation of Rac activities. In contrast, beta2 integrins induced stimulation of Cdc42 that was independent of Src family members. The PI 3-kinase dependency of beta2 integrin-mediated decrease in GTP-bound Rac could be explained by an enhanced Rac-GAP activity, since this activity was blocked by LY204002, whereas PP1 only had a minor effect. The fact that only Rac1 but not Rac2 (the dominating Rac) redistributed to the detergent-insoluble fraction and that it was independent of GTP loading excludes the possibility that down-regulation of Rac activities was due to depletion of GTP-bound Rac from the detergent-soluble fraction. The beta2 integrin-triggered relocalization of Rac1 to the cytoskeleton was enabled by a PI 3-kinase-induced dissociation of Rac1 from LyGDI. The dissociations of Rac1 and Rac2 from LyGDI also explained the PI 3-kinase-dependent translocations of Rac GTPases to the plasma membrane. However, these accumulations of Rac in the membrane, as well as that of p47phox and p67phox, were also regulated by Src tyrosine kinases. Inasmuch as Rac GTPases are part of the NADPH oxidase and the respiratory burst is elicited in neutrophils adherent by beta2 integrins, our results indicate that activation of the NADPH oxidase does not depend on the levels of Rac-GTP but instead requires a beta2 integrin-induced targeting of the Rac GTPases as well as p47phox and p67phox to the plasma membrane.

The role of BRCA1 in transcriptional regulation and cell cycle control

The exact functions of BRCA1 have not been fully described but it now seems apparent that it has roles in DNA damage repair, transcriptional regulation, cell cycle control and most recently in ubiquitylation. These functions of BRCA1 are most likely interdependent but this review will focus on the role of BRCA1 in relation to transcriptional regulation and in particular how this impacts upon cell cycle control. We will (i) describe the structure of BRCA1 and how it may contribute to its transcription function; (ii) describe the interaction of BRCA1 with the core transcriptional machinery (RNA polII); (iii) describe how BRCA1 may regulate transcription at an epigenetic level through chromatin modification; (iv) discuss the role of BRCA1 in modulating transcription through its association with sequence-specific transcription factors. Finally, we will discuss the possible effects of BRCA1 transcriptional regulation on downstream targets with known roles in cell cycle control.

Examining architects' performance in Nigeria private and public sectors building projects

Abstract: Purpose – The aim of this paper is to examine and compare the performance of architects with respect to clients' rating of importance over a set of performance criteria in Nigerian public and private sector building projects. Design/methodology/approach – A survey involving clients from both public and private sectors of recently completed building projects in Nigeria was undertaken. Data analysis includes comparing similarities and differences using standardised ratio, Mann Whitney U and Wilcoxon tests. Findings – The results show that private sector clients are likely to be more concerned with cost, while public sector clients are more concerned with buildability of design. A total of 79 per cent of the criteria were similarly selected by both sectors with respect to importance of the criteria. Architects need to improve their performance significantly in about 82 per cent of the whole set of 28 criteria. The architects performed better in the public sector than the private sector and 14 per cent of the criteria were indicated as being statistically different in terms of architects' performance. Originality/value – The results provide feedback which can be incorporated in architects' future projects so as to ensure successful project implementation in the building delivery process.

Characterization of the 5' upstream regulatory region of the human myostatin gene: regulation of myostatin gene transcription by dexamethasone in vitro

We cloned and characterized a 3.3-kb fragment containing the 5'-regulatory region of the human myostatin gene. The promoter sequence contains putative muscle growth response elements for glucocorticoid, androgen, thyroid hormone, myogenic differentiation factor 1, myocyte enhancer factor 2, peroxisome proliferator-activated receptor, and nuclear factor-kappaB. To identify sites important for myostatin's gene transcription and regulation, eight deletion constructs were placed in C(2)C(12) and L6 skeletal muscle cells. Transcriptional activity of the constructs was found to be significantly higher in myotubes compared with that of myoblasts. To investigate whether glucocorticoids regulate myostatin gene expression, we incubated both cell lines with dexamethasone. On both occasions, dexamethasone dose dependently increased both the promoter's transcriptional activity and the endogenous myostatin expression. The effects of dexamethasone were blocked when the cells were coincubated with the glucocorticoid receptor antagonist RU-486. These findings suggest that glucocorticoids upregulate myostatin expression by inducing gene transcription, possibly through a glucocorticoid receptor-mediated pathway. We speculate that glucocorticoid-associated muscle atrophy might be due in part to the upregulation of myostatin expression.