Modulation of the Chlamydia trachomatis In vitro transcriptome response by the sex hormones estradiol and progesterone

BACKGROUND:Chlamydia trachomatis is a major cause of sexually transmitted disease in humans. Previous studies in both humans and animal models of chlamydial genital tract infection have suggested that the hormonal status of the genital tract epithelium at the time of exposure can influence the outcome of the chlamydial infection. We performed a whole genome transcriptional profiling study of C. trachomatis infection in ECC-1 cells under progesterone or estradiol treatment.RESULTS:Both hormone treatments caused a significant shift in the sub-set of genes expressed (25% of the transcriptome altered by more than 2-fold). Overall, estradiol treatment resulted in the down-regulation of 151 genes, including those associated with lipid and nucleotide metabolism. Of particular interest was the up-regulation in estradiol-supplemented cultures of six genes (omcB, trpB, cydA, cydB, pyk and yggV), which suggest a stress response similar to that reported previously in other models of chlamydial persistence. We also observed morphological changes consistent with a persistence response. By comparison, progesterone supplementation resulted in a general up-regulation of an energy utilising response.CONCLUSION:Our data shows for the first time, that the treatment of chlamydial host cells with key reproductive hormones such as progesterone and estradiol, results in significantly altered chlamydial gene expression profiles. It is likely that these chlamydial expression patterns are survival responses, evolved by the pathogen to enable it to overcome the host's innate immune response. The induction of chlamydial persistence is probably a key component of this survival response.

Control, performance management systems and identification processes

Is it possible to control identities using performance management systems (PMSs)? This paper explores the theoretical fusion of management accounting and identity studies, providing a synthesised view of control, PMSs and identification processes. It argues that the effective use of PMSs generates a range of obtrusive mechanistic and unobtrusive organic controls that mediate identification processes to achieve a high level of identity congruency between individuals and collectives—groups and organisations. This paper contends that mechanistic control of PMSs provides sensebreaking effects and also creates structural conditions for sensegiving in top-down identification processes. These processes encourage individuals to continue the bottom-up processes of sensemaking, enacting identity and constructing identity narratives. Over time, PMS activities and conversations periodically mediate several episode(s) of identification to connect past, current and future identities. To explore this relationship, the dual locus of control—collectives and individuals—is emphasised to explicate their interplay. This multidisciplinary approach contributes to explaining the multidirectional effects of PMSs in obtrusive as well as unobtrusive ways, in order to control the nature of collectives and individuals in organisations.

Control, performance management system and identification processes

Is it possible to control identities using performance management systems (PMSs)? This paper explores the theoretical fusion of management accounting and identity studies, providing a synthesised view of control, PMSs and identification processes. It argues that the effective use of PMSs generates a range of obtrusive mechanistic and unobtrusive organic controls that mediate identification processes to achieve a high level of identity congruency between individuals and collectives—groups and organisations. This paper contends that mechanistic control of PMSs provides sensebreaking effects and also creates structural conditions for sensegiving in top-down identification processes. These processes encourage individuals to continue the bottom-up processes of sensemaking, enacting identity and constructing identity narratives. Over time, PMS activities and conversations periodically mediate several episode(s) of identification to connect past, current and future identities. To explore this relationship, the dual locus of control—collectives and individuals—is emphasised to explicate their interplay. This multidisciplinary approach contributes to explaining the multidirectional effects of PMSs in obtrusive as well as unobtrusive ways, in order to control the nature of collectives and individuals in organisations.

Problematising the processes of participation in networks : working through the rhetoric

Participation in networks, both as a concept and process, is widely supported in environmental education as a democratic and equitable pathway to individual and social change for sustainability. However, the processes of participation in networks are rarely problematized. Rather, it is assumed that we inherently know how to participate in networks. This assumption means that participation is seldom questioned. Underlying support for participation in networks is a belief that it allows individuals to connect in new and meaningful ways, that individuals can engage in making decisions and in bringing about change in arenas that affect them, and that they will be engaging in new, non-hierarchical and equitable relationships. In this paper we problematize participation in networks. As an example we use research into a decentralized network – described as such in its own literature - the Queensland Environmentally Sustainable Schools Initiative Alliance in Australia – to argue that while network participants were engaged and committed to participation in this network, 'old' forms of top-down engagement and relationships needed to be unlearnt. This paper thus proposes that for participation in decentralized networks to be meaningful, new learning about how to participate needs to occur.

Processpedia : an ecological environment for BPM stakeholders' collaboration

Purpose: The purpose of this paper is to clarify how end-users’ tacit knowledge can be captured and integrated in an overall business process management (BPM) approach. Current approaches to support stakeholders’ collaboration in the modelling of business processes envision an egalitarian environment where stakeholders interact in the same context, using the same languages and sharing the same perspectives on the business process. Therefore, such stakeholders have to collaborate in the context of process modelling using a language that some of them do not master, and have to integrate their various perspectives. Design/methodology/approach: The paper applies the SECI knowledge management process to analyse the problems of traditional top-down BPM approaches and BPM collaborative modelling tools. Besides, the SECI model is also applied to Wikipedia, a successful Web 2.0-based knowledge management environment, to identify how tacit knowledge is captured in a bottom-up approach. Findings – The paper identifies a set of requirements for a hybrid BPM approach, both top-down and bottom-up, and describes a new BPM method based on a stepwise discovery of knowledge. Originality/value: This new approach, Processpedia, enhances collaborative modelling among stakeholders without enforcing egalitarianism. In Processpedia tacit knowledge is captured and standardised into the organisation’s business processes by fostering an ecological participation of all the stakeholders and capitalising on stakeholders’ distinctive characteristics.

Wikileaks and the challenge of the “Fifth Estate”

The Time magazine ‘Person of theYear’ award is a venerable institution. Established by Time’s founder Henry Luce in 1927 as ‘Man of the Year’, it is an annual award given to ‘a person, couple, group, idea, place, or machine that ‘for better or for worse ... has done the most to influence the events of the year’ (Time 2002, p. 1). In 2010, the award was given to Mark Zuckerberg, the founder and CEO of the social networking site Facebook.There was, however, a strong campaign for the ‘People’s Choice’ award to be given to Julian Assange, the founder and editor-in-chief of Wikileaks, the online whistleblowing site. Earlier in the year Wikileaks had released more than 250 000 US government diplomatic cables through the internet, and the subsequent controver- sies around the actions of Wikileaks and Assange came to be known worldwide as ‘Cablegate’. The focus of this chapter is not on the implications of ‘Cablegate’ for international diplomacy, which continue to have great significance, but rather upon what the emergence of Wikileaks has meant for journalism, and whether it provides insights into the future of journalism. Both Facebook and Wikileaks, as well as social media platforms such as Twitter and YouTube, and independent media practices such as blogging, citizen journalism and crowdsourcing, are manifestations of the rise of social media, or what has also been termed web 2.0.The term ‘web 2.0’ was coined by Tim O’Reilly, and captures the rise of online social media platforms and services, that better realise the collaborative potential of digitally networked media. They do this by moving from the relatively static, top-down notions of interactivity that informed early internet development, towards more open and evolutionary models that better harness collective intelligence by enabling users to become the creators and collaborators in the development of online media content (Musser and O’Reilly 2007; Bruns 2008).

Proteasome activities decrease during dexamethasone-induced apoptosis of thymocytes

The induction of apoptosis in thymocytes by the glucocorticoid dexamethasone was used as a model system to investigate whether there are changes in 20 S and 26 S proteasome activities during apoptosis. We observed that thymocytes contain high concentrations of proteasomes and that following treatment with dexamethasone, cell extracts showed a decrease in proteasome chymotrypsin-like activity which correlated with the degree of apoptosis observed. The decrease in chymotrypsin-like activity of 20 S and 26S proteasomes was still apparent after these complexes had been partially puri®ed from apoptotic thymocyte extracts and was therefore not due to competition resulting from a general increase in protein turnover. The trypsin-like and peptidylglutamylpeptide hydrolase activities of proteasome complexes were also observed to decrease during apoptosis, but these decreases were reversed by the inhibition of apoptosis by the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp(OMe)-¯uoromethylketone. However, the chymotrypsin-like activity of proteasomes decreased further in the presence of the apoptosis inhibitor. Val-Ala-Asp-¯uoromethylketone was found to inhibit the chymotrypsin- and trypsin-like activity of 26 S proteasomes in .itro. The decrease in proteasome activities in apoptosis did not appear to be due to a decrease in the concentration of total cellular proteasomes. Thus, the early decreases in 20 S and 26 S proteasome activities during apoptosis appear to be due to a down-regulation of their proteolytic activities and not to a decrease in their protein concentration. These data suggest that proteasomes may be responsible, in thymocytes, for the turnover of a protein that functions as a positive regulator of apoptosis.

An investigation into the effect of amphiphilic siloxane oligomers on dermal fibroblasts

This study investigates the effect of well-defined poly(dimethylsiloxane)-poly(ethylene glycol) (PDMS-PEG) ABA linear block co-oligomers on the proliferation of human dermal fibroblasts. The co-oligomers assessed ranged in molecular weight (MW) from 1335 to 5208 Da and hydrophilic-lipophilic balance (HLB) from 5.9 to 16.6 by varying the number of both PDMS and PEG units. In general, it was found that co-oligomers of low MW or intermediate hydrophilicity significantly reduced fibroblast proliferation. A linear relationship between down-regulation of fibroblast proliferation, and the ratio HLB/MW was observed at concentrations of 0.1 and 1.0 wt % of the oligomers. This enabled the structures with highest efficiency to be determined. These results suggest the possible use of the PEG-PDMS-PEG block co-oligomers as an alternative to silicone gels for hypertrophic scar remediation.

Development issues for the creative economy in Malaysia

Cultural tourism and creative industries have intersecting policy agendas and economic interdependencies. Most studies of the creative industries have focused on western countries. Cultural tourism is rarely included. However the arrival of the creative economy and its movement through developing countries has changed the relationship. Supporters of the creative economy now see fit to include tourism. This thesis addresses the development of the creative economy in Malaysia. The thesis conducted case studies on animation and museum sectors in Malaysia. These two case studies provide information on the development of creative economy in Malaysia. The study found that a top-down cultural management approach is being practised but that Malaysia is now influenced by new ideas concerning innovation and technical creativity. The study examined whether or not technical innovation by itself is enough. The reference points here are the Multimedia Super Corridor in Cyberjaya and other similar projects in the region. The museum case study was situated in Malacca. It showed that museums needed to adapt new media and new experiences to remain relevant in today’s world. In applying a case study approach, the thesis made use of interviews with key stakeholders, as well consulting numerous policy documents and web sites. Both case studies imitated similar products and services in the market but added local characteristics. This research project contributes significantly to the existing body of knowledge in the field of creative economy within the context of developing countries. Finally the thesis makes recommendations for Malaysia to better position itself in the regional economy while retaining its distinctive cultural identity.

Development of a 3D culture system to study the skeletal metastasis of prostate cancer

In the cancer research field, most in vitro studies still rely on two-dimensional (2D) cultures. However, the trend is rapidly shifting towards using a three-dimensional (3D) culture system. This is because 3D models better recapitulate the microenvironment of cells, and therefore, yield cellular and molecular responses that more accurately describe the pathophysiology of cancer. By adopting technology platforms established by the tissue engineering discipline, it is now possible to grow cancer cells in extracellular matrix (ECM)-like environments and dictate the biophysical and biochemical properties of the matrix. In addition, 3D models can be modified to recapitulate different stages of cancer progression for instance from the initial development of tumor to metastasis. Inevitably, to recapitulate a heterotypic condition, comprising more than one cell type, it requires a more complex 3D model. To date, 3D models that are available for studying the prostate cancer (CaP)-bone interactions are still lacking. Therefore, the aim of this study is to establish a co-culture model that allows investigation of direct and indirect CaP-bone interactions. Prior to that, 3D polyethylene glycol (PEG)-based hydrogel cultures for CaP cells were first developed and growth conditions were optimised. Characterization of the 3D hydrogel cultures show that LNCaP cells form a multicellular mass that resembles avascular tumor. In comparison to 2D cultures, besides the difference in cell morphology, the response of LNCaP cells to the androgen analogue (R1881) stimulation is different compared to the cells in 2D cultures. This discrepancy between 2D and 3D cultures is likely associated with the cell-cell contact, density and ligand-receptor interactions. Following the 3D monoculture study, a 3D direct co-culture model of CaP cells and the human tissue engineered bone (hTEBC) construct was developed. Interactions between the CaP cells and human osteoblasts (hOBs) resulted in elevation of Matrix Metalloproteinase 9 (MMP9) for PC-3 cells and Prostate Specific Antigen (PSA) for LNCaP cells. To further investigate the paracrine interaction of CaP cells and (hOBs), a 3D indirect co-culture model was developed, where LNCaP cells embedded within PEG hydrogels were co-cultured with hTEBC. It was found that the cellular changes observed reflect the early event of CaP colonizing the bone site. In the absence of androgens, interestingly, up-regulation of PSA and other kallikreins is also detected in the co-culture compared to the LNCaP monoculture. This non androgenic stimulation could be triggered by the soluble factors secreted by the hOB such as Interleukin-6. There are also decrease in alkaline phosphatase (ALP) activity and down-regulation of genes of the hOB when co-cultured with LNCaP cells that have not been previously described. These genes include transforming growth factor β1 (TGFβ1), osteocalcin and Vimentin. However, no changes to epithelial markers (e.g E-cadherin, Cytokeratin 8) were observed in both cell types from the co-culture. Some of these intriguing changes observed in the co-cultures that had not been previously described have enriched the basic knowledge of the CaP cell-bone interaction. From this study, we have shown evidence of the feasibility and versatility of our established 3D models. These models can be adapted to test various hypotheses for studies pertaining to underlying mechanisms of bone metastasis and could provide a vehicle for anticancer drug screening purposes in the future.

School Leadership, Literacy and Social Justice : The Place of Local School Curriculum Planning and Reform

School reform is a matter of both redistributive social justice and recognitive social justice. Following Fraser (Justice interruptus: critical reflections on the “postsocialist” condition. Routledge, New York, 1997), we begin from a philosophical and political commitment to the more equitable redistribution of knowledge, credentials, competence, and capacity to children of low socioeconomic, cultural, and linguistic minority and Indigenous communities whose access, achievement, and participation historically have “lagged” behind system norms and benchmarks set by middle class and dominant culture communities. At the same time, we argue that the recognition of these students and their communities’ lifeworlds, knowledges, and experiences in the curriculum, in classroom teaching, and learning is both a means and an end: a means toward improved achievement measured conventionally and a goal for reform and alteration of mainstream curriculum knowledge and what is made to count in the school as valued cultural knowledge and practice. The work that we report here was based on an ongoing 4-year project where a team of university teacher educators/researchers have partnered with school leadership and staff to build relationships within community. The purpose has been to study whether and how engagement with new digital arts and multimodal literacies could have effects on students “conventional” print literacy achievement and, secondly, to study whether and how the overall performance of a school could be generated through a focus on professional conversations and partnerships in curriculum and instruction – rather than the top-down implementation of a predetermined pedagogical scheme, package, or approach.

Chemopreventive effect of PSP through targeting of prostate cancer stem cell-like population

Recent evidence suggested that prostate cancer stem/progenitor cells (CSC) are responsible for cancer initiation as well as disease progression. Unfortunately, conventional therapies are only effective in targeting the more differentiated cancer cells and spare the CSCs. Here, we report that PSP, an active component extracted from the mushroom Turkey tail (also known as Coriolus versicolor), is effective in targeting prostate CSCs. We found that treatment of the prostate cancer cell line PC-3 with PSP led to the down-regulation of CSC markers (CD133 and CD44) in a time and dose-dependent manner. Meanwhile, PSP treatment not only suppressed the ability of PC-3 cells to form prostaspheres under non-adherent culture conditions, but also inhibited their tumorigenicity in vivo, further proving that PSP can suppress prostate CSC properties. To investigate if the anti-CSC effect of PSP may lead to prostate cancer chemoprevention, transgenic mice (TgMAP) that spontaneously develop prostate tumors were orally fed with PSP for 20 weeks. Whereas 100% of the mice that fed with water only developed prostate tumors at the end of experiment, no tumors could be found in any of the mice fed with PSP, suggesting that PSP treatment can completely inhibit prostate tumor formation. Our results not only demonstrated the intriguing anti-CSC effect of PSP, but also revealed, for the first time, the surprising chemopreventive property of oral PSP consumption against prostate cancer.

Differential expression of chemokine and matrix re-modelling genes is associated with contrasting schistosome-induced hepatopathology in murine models

The pathological outcomes of schistosomiasis are largely dependent on the molecular and cellular mechanisms of the host immune response. In this study, we investigated the contribution of variations in host gene expression to the contrasting hepatic pathology observed between two inbred mouse strains following Schistosoma japonicum infection. Whole genome microarray analysis was employed in conjunction with histological and immunohistochemical analysis to define and compare the hepatic gene expression profiles and cellular composition associated with the hepatopathology observed in S. japonicum-infected BALB/c and CBA mice. We show that the transcriptional profiles differ significantly between the two mouse strains with high statistical confidence. We identified specific genes correlating with the more severe pathology associated with CBA mice, as well as genes which may confer the milder degree of pathology associated with BALB/c mice. In BALB/c mice, neutrophil genes exhibited striking increases in expression, which coincided with the significantly greater accumulation of neutrophils at granulomatous regions seen in histological sections of hepatic tissue. In contrast, up-regulated expression of the eosinophil chemokine CCL24 in CBA mice paralleled the cellular influx of eosinophils to the hepatic granulomas. Additionally, there was greater down-regulation of genes involved in metabolic processes in CBA mice, reflecting the more pronounced hepatic damage in these mice. Profibrotic genes showed similar levels of expression in both mouse strains, as did genes associated with Th1 and Th2 responses. However, imbalances in expression of matrix metalloproteinases (e.g. MMP12, MMP13) and tissue inhibitors of metalloproteinases (TIMP1) may contribute to the contrasting pathology observed in the two strains. Overall, these results provide a more complete picture of the molecular and cellular mechanisms which govern the pathological outcome of hepatic schistosomiasis. This improved understanding of the immunopathogenesis in the murine model schistosomiasis provides the basis for a better appreciation of the complexities associated with chronic human schistosomiasis.

Does metabolic compensation explain the majority of less-than-expected weight loss in obese adults during a short-term severe diet and exercise intervention?

Objective: We investigated to what extent changes in metabolic rate and composition of weight loss explained the less-than-expected weight loss in obese men and women during a diet-plus-exercise intervention. Design: 16 obese men and women (41 ± 9 years; BMI 39 ± 6 kg/m2) were investigated in energy balance before, after and twice during a 12-week VLED (565–650 kcal/day) plus exercise (aerobic plus resistance training) intervention. The relative energy deficit (EDef) from baseline requirements was severe (74-87%). Body composition was measured by deuterium dilution and DXA and resting metabolic rate (RMR) by indirect calorimetry. Fat mass (FM) and fat-free mass (FFM) were converted into energy equivalents using constants: 9.45 kcal/gFM and 1.13 kcal/gFFM. Predicted weight loss was calculated from the energy deficit using the '7700 kcal/kg rule'. Results: Changes in weight (-18.6 ± 5.0 kg), FM (-15.5 ± 4.3 kg), and FFM (-3.1 ± 1.9 kg) did not differ between genders. Measured weight loss was on average 67% of the predicted value, but ranged from 39 to 94%. Relative EDef was correlated with the decrease in RMR (R=0.70, P<0.01) and the decrease in RMR correlated with the difference between actual and expected weight loss (R=0.51, P<0.01). Changes in metabolic rate explained on average 67% of the less-than-expected weight loss, and variability in the proportion of weight lost as FM accounted for a further 5%. On average, after adjustment for changes in metabolic rate and body composition of weight lost, actual weight loss reached 90% of predicted values. Conclusion: Although weight loss was 33% lower than predicted at baseline from standard energy equivalents, the majority of this differential was explained by physiological variables. While lower-than-expected weight loss is often attributed to incomplete adherence to prescribed interventions, the influence of baseline calculation errors and metabolic down-regulation should not be discounted.

A Nobel Prize for governance and institutions : Oliver Williamson and Elinor Ostrom

This paper reviews the 2009 Nobel Prize in Economics jointly awarded to Oliver Williamson for his work on governance in organizations and the boundaries of the firm, and to Elinor Ostrom for her work on the governance of common pool resources. We review the careers and the research contributions of Williamson and Ostrom to the theory and analysis of economic institutions of governance. Both winners of this Prize for 'economic governance' are thoroughly deserved, yet like the Hayek- Myrdal Prize of 1974 their respective approaches, methods and findings are almost diametrically opposed. Williamson offers a top-down contracts-based solution to the incentive problems of opportunism in corporate governance, whereas Ostrom offers a bottom-up communication-based solution to the governance opportunities of community resources. We offer some critical comments on Williamson's analytic work and discussion of the potential for further application of Ostrom's case-study based experimental methodology. We conclude with a suggested third nominee to make better sense of how these two great scholars' works fit together, namely George Richardson'