Intranasal immunization with C. muridarum major outer membrane protein (MOMP) and cholera toxin elicits local production of neutralising IgA in the prostate

Successful control of sexually transmitted diseases (STDs) through vaccination will require the development of vaccine strategies that target protective immunity to both the female and male reproductive tracts (MRT). In the male, the immune privileged nature of the male reproductive tract provides a barrier to entry of serum immunoglobulins into the male reproductive ducts, thereby preventing the induction of protective immunity using conventional injectable vaccination techniques. In this study we investigated the potential of intranasal (IN) immunization to elicit anti-chlamydial immunity in BALB/c male mice. Intranasal immunization with Chlamydia muridarum major outer membrane protein (MOMP) admixed with cholera toxin (CT) resulted in high levels of MOMP-specific IgA in prostatic fluids (PF) and MOMP-specific IgA-secreting cells in the prostate. Prostatic fluid IgA inhibited in vitro infection of McCoy cells with C. muridarum. Using RT-PCR we also show that mRNA for the polymeric immunoglobulin receptor (PIgR), which transports IgA across mucosal epithelia, is expressed only in the prostate but not in other regions of the male reproductive ducts upstream of the prostate. These data suggest that using intranasal immunization to target IgA to the prostate may protect males against STDs while at the same time maintaining the state of immune privilege within the MRT.

The distribution of absorptive capacity among construction supply chain participants

The absorptive capacity of organisations is one of the key drivers of innovation performance in any industry. This research seeks to refine our understanding of the relationship between absorptive capacity and innovation performance, with a focus on characterising the absorptive capacity of the different participant groups within the Australian road industry supply chain. One of the largest and most comprehensive surveys ever undertaken of innovation in road construction was completed in 2011 by the Queensland University of Technology (QUT), based on the Australian road industry. The survey of over 200 construction industry participants covered four sectors, comprising suppliers (manufacturers and distributors), consultants (engineering consultants), contractors (head and subcontractors) and clients (state government road agencies). The survey measured the absorptive capacity and innovation activity exhibited by organisations within each of these participant groups, using the perceived importance of addressing innovation obstacles as a proxy for innovation activity. One of the key findings of the survey is about the impact of participant competency on product innovation activity. The survey found that the absorptive capacity of industry participants had a significant and positive relationship with innovation activity. Regarding the distribution of absorptive capacity, the results indicate that suppliers are more likely to have high levels of absorptive capacity than the other participant groups, with 32% of suppliers showing high absorptive capacity, ahead of contractors (18%), consultants (11%), and clients (7%). These results support the findings of previous studies in the literature and suggest the importance of policies to enhance organisational learning, particularly in relation to openness to new product ideas.

A short-term production scheduling methodology for open-pit mines

A multi-resource multi-stage scheduling methodology is developed to solve short-term open-pit mine production scheduling problems as a generic multi-resource multi-stage scheduling problem. It is modelled using essential characteristics of short-term mining production operations such as drilling, sampling, blasting and excavating under the capacity constraints of mining equipment at each processing stage. Based on an extended disjunctive graph model, a shifting-bottleneck-procedure algorithm is enhanced and applied to obtain feasible short-term open-pit mine production schedules and near-optimal solutions. The proposed methodology and its solution quality are verified and validated using a real mining case study.

Interleukin-1β stimulates human renal fibroblast proliferation and matrix protein production by means of a transforming growth factor-β-dependent mechanism

One of the hallmarks of progressive renal disease is the development of tubulointerstitial fibrosis. This is frequently preceded by macrophage infiltration, raising the possibility that macrophages relay fibrogenic signals to resident tubulointerstitial cells. The aim of this study was to investigate the potentially fibrogenic role of interleukin-1beta (IL-1beta), a macrophage-derived inflammatory cytokine, on cortical fibroblasts (CFs). Primary cultures of human renal CFs were established and incubated for 24 hours in the presence or absence of IL-1beta. We found that IL-1beta significantly stimulated DNA synthesis (356.7% +/- 39% of control, P <.003), fibronectin secretion (261.8 +/- 11% of control, P <.005), collagen type 1 production, (release of procollagen type 1 C-terminal-peptide, 152.4% +/- 26% of control, P <.005), transforming growth factor-beta (TGF-beta) secretion (211% +/- 37% of control, P <.01), and nitric oxide (NO) production (342.8% +/- 69% of control, P <.002). TGF-beta (1 ng/mL) and the phorbol ester phorbol 12-myristate 13-acetate (PMA, 25 nmol/L) produced fibrogenic effects similar to those of IL-1beta. Neither a NO synthase inhibitor (N(G)-methyl-l-arginine, 1 mmol/L) nor a protein kinase C (PKC) inhibitor (bis-indolylmaleimide 1, 1 micromol/L) altered the enhanced level of fibronectin secretion or DNA synthesis seen in response to IL-1beta treatment. However, addition of a TGF-beta-neutralizing antibody significantly reduced IL-1beta-induced fibronectin secretion (IL-1beta + IgG, 262% +/- 72% vs IL-1beta + alphaTGF-beta 156% +/- 14%, P <.02), collagen type 1 production (IL-1beta + IgG, 176% +/- 28% vs IL-1beta + alphaTGF-beta, 120% +/- 14%, P <.005) and abrogated IL-1beta-induced DNA synthesis (245% +/- 49% vs 105% +/- 21%, P <.005). IL-1beta significantly stimulated CF DNA synthesis and production of fibronectin, collagen type 1, TGFbeta, and NO. The fibrogenic and proliferative action of IL-1beta on CF appears not to involve activation of PKC or production of NO but is at least partly TGFbeta-dependent.

Interleukin-1beta induces human proximal tubule cell injury, alpha-smooth muscle actin expression and fibronectin production

BACKGROUND Tubulointerstitial lesions, characterized by tubular injury, interstitial fibrosis and the appearance of myofibroblasts, are the strongest predictors of the degree and progression of chronic renal failure. These lesions are typically preceded by macrophage infiltration of the tubulointerstitium, raising the possibility that these inflammatory cells promote progressive renal disease through fibrogenic actions on resident tubulointerstitial cells. The aim of the present study, therefore, was to investigate the potentially fibrogenic mechanisms of interleukin-1beta (IL-1beta), a macrophage-derived pro-inflammatory cytokine, on human proximal tubule cells (PTC). METHODS Confluent, quiescent, passage 2 PTC were established in primary culture from histologically normal segments of human renal cortex (N = 11) and then incubated in serum- and hormone-free media supplemented with either IL-1beta (0 to 4 ng/mL) or vehicle (control). RESULTS IL-1beta significantly enhanced fibronectin secretion by up to fourfold in a time- and concentration-dependent fashion. This was accompanied by significant (2.5- to 6-fold) increases in alpha-smooth muscle actin (alpha-SMA) expression, transforming growth factor beta (TGF-beta1) secretion, nitric oxide (NO) production, NO synthase 2 (NOS2) mRNA and lactate dehydrogenase (LDH) release. Cell proliferation was dose-dependently suppressed by IL-1beta. NG-methyl-l-arginine (L-NMMA; 1 mmol/L), a specific inhibitor of NOS, blocked NO production but did not alter basal or IL-1beta-stimulated fibronectin secretion. In contrast, a pan-specific TGF-beta neutralizing antibody significantly blocked the effects of IL-1beta on PTC fibronectin secretion (IL-1beta, 268.1 +/- 30.6 vs. IL-1beta+alphaTGF-beta 157.9 +/- 14.4%, of control values, P < 0.001) and DNA synthesis (IL-1beta 81.0 +/- 6.7% vs. IL-1beta+alphaTGF-beta 93.4 +/- 2.1%, of control values, P < 0.01). CONCLUSION IL-1beta acts on human PTC to suppress cell proliferation, enhance fibronectin production and promote alpha-smooth muscle actin expression. These actions appear to be mediated by a TGF-beta1 dependent mechanism and are independent of nitric oxide release.

Talk about a YouTube video in preschool : the mutual production of shared understanding for learning with digital technology

Much of what is written about digital technologies in preschool contexts focuses on young children’s acquisition of skills rather than their meaning-making during use of technologies. In this paper, we consider how the viewing of a YouTube video was used by a teacher and children to produce shared understandings about it. Conversation analysis of talk and interaction during the viewing of the video establishes some of the ways that individual accounts of events were produced for others and then endorsed as shared understandings. The analysis establishes how adults and children made use of verbal and embodied actions during interactions to produce shared understandings of the YouTube video, the events it recorded and written commentary about those events

IL-23R is epigenetically regulated and modulated by chemotherapy in non-small cell lung cancer

The Interleukin-23 (IL-23)/IL-23R signaling axis is an important inflammatory pathway, involved in the stimulation and regulation of the T helper (Th) 17 lymphocytes, resulting in the production of IL-17. Aside from auto-immunity, this cytokine has also been linked to carcinogenesis and polymorphisms in the IL-23R gene are associated with an increased risk for the development of a number of different cancers. Activation of the IL-23 pathway results in the up-regulation of STAT3 and it is thought that the pathological consequences associated with this are in part due to the production of IL-17. We have previously identified IL-23A as pro-proliferative and epigenetically regulated in non-small cell lung cancer (NSCLC). The current study aims to evaluate IL-23R in greater detail in NSCLC. We demonstrate that IL-23R is expressed and epigenetically regulated in NSCLC through histone post-translation modifications and CpG island methylation. In addition, Gemcitabine treatment, a chemotherapy drug used in the treatment of NSCLC, resulted in the up-regulation of the IL-23R. Furthermore, Apilimod (STA 5326), a small molecule which blocks the expression of IL-23 and IL-12, reduced the proliferative capacity of NSCLC cells, particularly in the adenocarcinoma (A549) sub-type. Apilimod is currently undergoing investigation in a number of clinical trials for the treatment of auto-immune conditions such as Crohn's disease and Rheumatoid Arthritis. Our results may have implications for treating NSCLC patients with Gemcitabine or epigenetic targeted therapies. However, Apilimod may possibly provide a new treatment avenue for NSCLC patients. Work is currently ongoing to further delineate the IL-23/IL-23R axis in this disease.

Estrogen receptor β activation impairs mitochondrial oxidative metabolism and affects malignant mesothelioma cell growth in vitro and in vivo

Estrogen receptor (ER)-β has been shown to possess a tumor suppressive effect, and is a potential target for cancer therapy. Using gene-expression meta-analysis of human malignant pleural mesothelioma, we identified an ESR2 (ERβ coding gene) signature. High ESR2 expression was strongly associated with low succinate dehydrogenase B (SDHB) (which encodes a mitochondrial respiratory chain complex II subunit) expression. We demonstrate that SDHB loss induced ESR2 expression, and that activated ERβ, by over-expression or by selective agonist stimulation, negatively affected oxidative phosphorylation compromising mitochondrial complex II and IV activity. This resulted in reduced mitochondrial ATP production, increased glycolysis dependence and impaired cell proliferation. The observed in vitro effects were phenocopied in vivo using a selective ERβ agonist in a mesothelioma mouse model. On the whole, our data highlight an unforeseen interaction between ERβ-mediated tumor suppression and energy metabolism that may be exploited to improve on the therapy for clinical management of malignant mesothelioma.

Music production in times of monopoly : the example of Sweden

For several decades now, Sweden has been successful in the worldwide popular music arena. This article explores how Sweden, as an integral part of the global music industry, has been able to cope with the changed market conditions brought about by regulatory changes and digital technologies. The article reflects on the virtualization of music distribution, the decline of the long‐play album and the ageing popular music audience.

Investigating relationships between relationship quality, customer loyalty and cooperation : an empirical study of convenience stores' franchise chain systems

Franchising has become a way to minimise the risks of small business management. There has been little research into the factors that promote franchise relationship success. This study attempts to empirically examine the important elements (relationship quality, customer loyalty and cooperation), which might promote a successful long-term franchising relationship between franchisors and franchisees within the context of convenience stores in Taiwan. A model of these relationships was developed and tested. A total of 500 surveys were mailed to a random sample of convenience stores’ franchisee owners among the four main franchisors in Taiwan. The results show that relationship quality positively influences the cooperation between franchisors and franchisees and is positively correlated with franchisee loyalty. Additionally, the cooperative behaviour between franchisees and franchisors is significantly associated with franchisees’ loyalty.

Literacies on the Web : Co-Production of Literary Texts on Fan Fiction Sites

In this chapter the authors discuss and informal learning settings such as fan fiction sites and their relations to teaching and learning within formal learning settings. Young people today spend a lot of time with social media built on user generated content. These media are often characterized by participatory culture which offers a good environment for developing skills and identity work. In this chapter the authors problematize fan fiction sites as informal learning settings where the possibilities to learn are powerful and significant. They also discuss the learning processes connected to the development of literacies. Here the rhetoric principle of “imitatio” plays a vital part as well as the co-production of texts on the sites, strongly supported by the beta reader and the power of positive feedback. They also display that some fans, through the online publication of fan fiction, are able to develop their craft in a way which previously have been impossible.

Myosin light chain kinase regulates synaptic plasticity and fear learning in the lateral amygdala

Learning and memory depend on signaling mole- cules that affect synaptic efficacy. The cytoskeleton has been implicated in regulating synaptic transmission but its role in learning and memory is poorly understood. Fear learning depends on plasticity in the lateral nucleus of the amygdala. We therefore examined whether the cytoskeletal-regulatory protein, myosin light chain kinase, might contribute to fear learning in the rat lateral amygdala. Microinjection of ML-7, a specific inhibitor of myosin light chain kinase, into the lateral nucleus of the amygdala before fear conditioning, but not immediately afterward, enhanced both short-term memory and long-term memory, suggesting that myosin light chain kinase is involved specifically in memory acquisition rather than in posttraining consolidation of memory. Myosin light chain kinase inhibitor had no effect on memory retrieval. Furthermore, ML-7 had no effect on behavior when the train- ing stimuli were presented in a non-associative manner. An- atomical studies showed that myosin light chain kinase is present in cells throughout lateral nucleus of the amygdala and is localized to dendritic shafts and spines that are postsynaptic to the projections from the auditory thalamus to lateral nucleus of the amygdala, a pathway specifically impli- cated in fear learning. Inhibition of myosin light chain kinase enhanced long-term potentiation, a physiological model of learning, in the auditory thalamic pathway to the lateral nu- cleus of the amygdala. When ML-7 was applied without as- sociative tetanic stimulation it had no effect on synaptic responses in lateral nucleus of the amygdala. Thus, myosin light chain kinase activity in lateral nucleus of the amygdala appears to normally suppress synaptic plasticity in the cir- cuits underlying fear learning, suggesting that myosin light chain kinase may help prevent the acquisition of irrelevant fears. Impairment of this mechanism could contribute to pathological fear learning.

A Review On The Production Of Levulinic Acid And Furanics From Sugars

Sugarcane products represent an abundant and relatively low cost carbon resource that can be utilised to produce chemical intermediates such as levulinic acid and furanics. These chemicals can be easily upgraded to commodity and specialty chemicals and biofuels by high yielding and well established technologies. However, there are challenges and technical hurdles that need to be overcome before these chemical intermediates can be cost-effectively produced in commercial quantities. The paper reviews production of levulinic acid and furanics from sugars by homogeneous mineral acid catalysts, and reports on preliminary studies on the production of these compounds with environmentally friendly biodegradable sulfonic acids. The yields (>50% of theoretical) of levulinic acid, formic acid and furfural obtained with these organic acids are comparable to that of sulphuric acid currently used for their production.

The Empty City (production)

This creative work is the production of the live and animated performance of The Empty City. With a significant period of creative development and script work behind it, the team engaged in a range of innovative performance-making practices in order to realise the work onstage as a non-verbal live and animated theatre work. This intermedial process was often led by music, and involved the creation and convergence of non-verbal action, virtual performers, performing objects and two simultaneous projections of animated images. The production opened at the Brisbane Powerhouse on June 27 2013, with a subsequent tour to Perth’s Awesome Festival in October 2013. Its technical achievements were noted in the critical responses. "The story is told on a striking set of two huge screens, the front one transparent, upon which still and moving images are projected, and between which Oliver performs and occasional “real” objects are placed. The effect is startling, and creates a cartoon three dimensionality like those old Viewmaster slide shows. The live action… and soundscape sync perfectly with the projected imagery to complete a dense, intricately devised and technically brilliant whole." (The West Australian 14.10.13)

Urban Food Security, Urban Resilience and Climate Change

The growing importance of logistics in increasingly globalised production and consumption systems strengthens the case for explicit consideration of the climate risks that may impact on the operation of ports in the future, as well as the formulation of adaptation responses that act to enhance their resilience. Within a logistics chain, seaports are functional nodes of significant strategic importance, and are considered as critical gateways linking local and national supply chains to global markets. However, they are more likely to be exposed to vagaries of climate-related extreme events due to their coastal locations. As such, they need to be adaptive and respond to the projected impacts of climate change, in particular extreme weather events. These impacts are especially important in the logistics context as they could result in varying degrees of business interruption; including business closure in the worst case scenario. Since trans-shipment of freight for both the import and export of goods and raw materials has a significant impact on Australia’s sustained economic growth it was considered important to undertake a study of port functional assets, to assess their vulnerability to climate change, to model the potential impacts of climate-related extreme events, and to highlight possible adaptation responses.