Matrix metalloproteinase-9 of tubular and macrophage origin contributes to the pathogenesis of renal fibrosis via macrophage recruitment through osteopontin cleavage

A pro-fibrotic role of matrix metalloproteinase-9 (MMP-9) in tubular cell epithelial-mesenchymal transition (EMT) is well established in renal fibrosis; however studies from our group and others have demonstrated some previously unrecognized complexity of MMP-9 that has been overlooked in renal fibrosis. Therefore, the aim of this study was to determine the expression pattern, origin and the exact mechanism underlying the contribution of MMP-9 to unilateral ureteral obstruction (UUO), a well-established model of renal fibrosis via MMP-9 inhibition. Renal MMP-9 expression in BALB/c mice with UUO was examined on day 1, 3, 5, 7, 9, 11 and 14. To inhibit MMP-9 activity, MMP-2/9 inhibitor or MMP-9-neutralizing antibody was administered daily for 4 consecutive days from day 0-3, 6-9 or 10-13 and tissues harvested at day 14. In UUO, there was a bi-phasic early- and late-stage upregulation of MMP-9 activity. Interestingly, tubular epithelial cells (TECs) were the predominant source of MMP-9 during early stage, whereas TECs, macrophages and myofibroblasts produced MMP-9 during late-stage UUO. Early- and late-stage inhibition of MMP-9 in UUO mice significantly reduced tubular cell EMT and renal fibrosis. Moreover, MMP-9 inhibition caused a significant reduction in MMP-9-cleaved osteopontin and macrophage infiltration in UUO kidney. Our in vitro study showed MMP-9-cleaved osteopontin enhanced macrophage transwell migration and MMP-9 of both primary TEC and macrophage induced tubular cell EMT. In summary, our result suggests that MMP-9 of both TEC and macrophage origin may directly or indirectly contribute to the pathogenesis of renal fibrosis via osteopontin cleavage, which, in turn further recruit macrophage and induce tubular cell EMT. Our study also highlights the time dependency of its expression and the potential of stage-specific inhibition strategy against renal fibrosis.

Discussion on full-scale internal pressure measurements

The wind loading on most structural elements is made up of both an external and internal pressure. Internal pressures are also important for the design of naturally ventilated buildings. The internal pressure is the interaction between the external pressure propagating through the building envelope and any internal plant causing building pressurization. Although the external pressure field can be well defined through a series of wind tunnel tests, modeling complexities makes accurate prediction of the internal pressure difficult. For commercial testing for the determination of design cladding pressures, an internal pressure coefficient is generally assumed from wind loading standards. Several theories regarding the propagation of internal pressures through single and multiple dominant openings have been proposed for small and large flexible buildings (Harris (1990), Holmes, (1979), Liu & Saathoff (1981 ), Vickery (1986, 1994), Vickery & Bloxham (1992), Vickery & Georgiou (1991))...

Effect of broadcast baiting on abundance patterns of red imported fire ants (Hymenoptera: Formicidae) and key local ant genera at long-term monitoring sites in Brisbane, Australia

In 2001, the red imported fire ant (Solenopsis invicta Buren) was identified in Brisbane, Australia. An eradication program involving broadcast bait treatment with two insect growth regulators and a metabolic inhibitor began in September of that year and is currently ongoing. To gauge the impacts of these treatments on local ant populations, we examined long-term monitoring data and quantified abundance patterns of S. invicta and common local ant genera using a linear mixed-effects model. For S. invicta, presence in pitfalls reduced over time to zero on every site. Significantly higher numbers of S. invicta workers were collected on high-density polygyne sites, which took longer to disinfest compared with monogyne and low-density polygyne sites. For local ants, nine genus groups of the 10 most common genera analyzed either increased in abundance or showed no significant trend. Five of these genus groups were significantly less abundant at the start of monitoring on high-density polygyne sites compared with monogyne and low-density polygyne sites. The genus Pheidole significantly reduced in abundance over time, suggesting that it was affected by treatment efforts. These results demonstrate that the treatment regime used at the time successfully removed S. invicta from these sites in Brisbane, and that most local ant genera were not seriously impacted by the treatment. These results have important implications for current and future prophylactic treatment efforts, and suggest that native ants remain in treated areas to provide some biological resistance to S. invicta.

Attracting and Retaining Staff : The Role of Branding and Industry Image

In increasingly competitive labour markets, attracting and retaining talent has become a prime concern of organisations. Employers need to understand the range of factors that influence career decision making and the role of employer branding in attracting human capital that best fits and contributes to the strategic aims of an organisation. This chapter identifies the changing factors that attract people to certain employment and industries and discusses the importance of aligning employer branding with employee branding to create a strong, genuine and lasting employer brand. Whilst organisations have long used marketing and branding practices to engender loyalty in customers, they are increasingly expanding this activity to differentiate organisations and make them attractive from an employee perspective. This chapter discusses employer branding and industry image as two important components of attraction strategies and describes ways companies can maximise their brand awareness in the employment market to both current and future employees.

Helpline Discourse

Helplines are services where callers can request help, advice, information, or support. While such help is usually offered through telephone helplines, web chat and email helplines are becoming increasingly available to members of the public. Helplines tend to offer specialized services, such as responding to computer software queries, or medical and health issues, or seeking information about natural disasters. Further, they may be aimed at particular populations such as children and young people. The earliest research investigating discourse in calls to helplines in social interactional research began in the 1960s with Sacks’ early work on calls to a suicide prevention center. Since then interactional research has produced a wealth of understandings into the mundane and institutional interactional practices through which help is sought and delivered. In addition to discussing the breadth of research into helplines, this entry explores the relationship between philosophies and interactional practices of helpline services.

A large proportion of asymptomatic Plasmodium infections with low and sub-microscopic parasite densities in the low transmission setting of Temotu Province, Solomon Islands : challenges for malaria diagnostics in an elimination setting

Background Many countries are scaling up malaria interventions towards elimination. This transition changes demands on malaria diagnostics from diagnosing ill patients to detecting parasites in all carriers including asymptomatic infections and infections with low parasite densities. Detection methods suitable to local malaria epidemiology must be selected prior to transitioning a malaria control programme to elimination. A baseline malaria survey conducted in Temotu Province, Solomon Islands in late 2008, as the first step in a provincial malaria elimination programme, provided malaria epidemiology data and an opportunity to assess how well different diagnostic methods performed in this setting. Methods During the survey, 9,491 blood samples were collected and examined by microscopy for Plasmodium species and density, with a subset also examined by polymerase chain reaction (PCR) and rapid diagnostic tests (RDTs). The performances of these diagnostic methods were compared. Results A total of 256 samples were positive by microscopy, giving a point prevalence of 2.7%. The species distribution was 17.5% Plasmodium falciparum and 82.4% Plasmodium vivax. In this low transmission setting, only 17.8% of the P. falciparum and 2.9% of P. vivax infected subjects were febrile (≥38°C) at the time of the survey. A significant proportion of infections detected by microscopy, 40% and 65.6% for P. falciparum and P. vivax respectively, had parasite density below 100/μL. There was an age correlation for the proportion of parasite density below 100/μL for P. vivax infections, but not for P. falciparum infections. PCR detected substantially more infections than microscopy (point prevalence of 8.71%), indicating a large number of subjects had sub-microscopic parasitemia. The concordance between PCR and microscopy in detecting single species was greater for P. vivax (135/162) compared to P. falciparum (36/118). The malaria RDT detected the 12 microscopy and PCR positive P. falciparum, but failed to detect 12/13 microscopy and PCR positive P. vivax infections. Conclusion Asymptomatic malaria infections and infections with low and sub-microscopic parasite densities are highly prevalent in Temotu province where malaria transmission is low. This presents a challenge for elimination since the large proportion of the parasite reservoir will not be detected by standard active and passive case detection. Therefore effective mass screening and treatment campaigns will most likely need more sensitive assays such as a field deployable molecular based assay.

A Study of feature extraction algorithms for optical flow tracking

Sparse optical flow algorithms, such as the Lucas-Kanade approach, provide more robustness to noise than dense optical flow algorithms and are the preferred approach in many scenarios. Sparse optical flow algorithms estimate the displacement for a selected number of pixels in the image. These pixels can be chosen randomly. However, pixels in regions with more variance between the neighbours will produce more reliable displacement estimates. The selected pixel locations should therefore be chosen wisely. In this study, the suitability of Harris corners, Shi-Tomasi's “Good features to track", SIFT and SURF interest point extractors, Canny edges, and random pixel selection for the purpose of frame-by-frame tracking using a pyramidical Lucas-Kanade algorithm is investigated. The evaluation considers the important factors of processing time, feature count, and feature trackability in indoor and outdoor scenarios using ground vehicles and unmanned aerial vehicles, and for the purpose of visual odometry estimation.

What do young Australian engineers want? Strategies to attract this talent to less glamorous industries

Chapters in Book 1 of this two-volume set explored literature pertaining to the shortage of engineers in Australia, the ageing engineering workforce, issues of skilled migration, and career development and pathways. The companion chapter to this one in Book 1 explored attraction and image issues of certain industries that required a pipeline of engineers. This chapter will reflect on our research with final-year engineering students in Australian universities and TAFE colleges regarding their career aspirations, industries and/or organisations that they identify as attractive employers, and their perceptions of a low-profile industry, namely the Australian rail industry. This chapter will also discuss specific, evidence-based strategies and activities to enhance the image and attraction of low-profile industries.

What makes e-learning work?

This chapter examines lessons learnt from a study of the use of e-learning within the rail sector in Australia and explores factors that inhibit or advance its organisational effectiveness. We examine the social, organisational and technical influences on the way employees perceive and use e-learning. By examining these issues, we aim to demonstrate that successful organisational adoption of e-learning is influenced by factors beyond the systems themselves and requires a more holistic understanding of the target workforce and the suitability of the e-learning tasks. Without a clear understanding of these relationships, organisations run the real risk of investing heavily in e-learning without receiving benefits or, worse still, impacting negatively on their ability to deliver training.

Deviant consumer behaviour : a qualitative exploration

Deviant behaviour is an ongoing problem in the consumer marketplace (Daunt and Harris, 2012). To investigate this issue, a number of authors have focused on empirically assessing consumer perceptions of right and wrong behaviours, such as the Muncy-Vitell (1992) consumer ethics scale. While studies like this have provided extensive empirical insights, qualitative insight into why consumers make these behaviour classifications remains underexplored. The aim of this paper is to extend on that literature by exploring the reasoning behind behavioural classifications. Using interviews, seven factors were identified in consumer definitions of acceptable, questionable, and unacceptable consumer behaviours including; official classification, prevalence, ease of justification, perceived fairness, consequences, risk, and values. These results also provide actionable insights for marketers in that multi-level deterrence strategies must be employed to more effectively deter consumer deviance, as opposed to traditional deterrence strategies based on cost-benefit analyses.

Interactions of ingested food, beverage, and tobacco components involving human cytochrome P4501A2, 2A6, 2E1, and 3A4 enzymes

Human cytochrome P450 (P450) enzymes are involved in the oxidation of natural products found in foods, beverages, and tobacco products and their catalytic activities can also be modulated by components of the materials. The microsomal activation of aflatoxin B1 to the exo-3,9-epoxide is stimulated by flavone and 7,8-benzoflavone, and attenuated by the flavonoid naringenin, a major component of grapefruit. P4502E1 has been demonstrated to play a potentially major role in the activation of a number of very low-molecular weight cancer suspects, including ethyl carbamate (urethan), which is present in alcoholic beverages and particularly stone brandies. The enzyme (P4502E1) is also known to be inducible by ethanol. Tobacco contains a large number of potential carcinogens. In human liver microsomes a significant role for P4501A2 can be demonstrated in the activation of cigarette smoke condensate. Some of the genotoxicity may be due to arylamines. P4501A2 is also inhibited by components of crude cigarette smoke condensate. The tobacco-specific nitrosamines are activated by a number of P450 enzymes. Of those known to be present in human liver, P4501A2, 2A6, and 2E1 can activate these nitrosamines to genotoxic products.

Activation of toxic chemicals by cytochrome P450 enzymes : regio- and stereoselective oxidation of aflatoxin B1

Cytochrome P450 (P450) enzymes are involved in the oxidations of numerous steroids, eicosanoids, alkaloids, and other endogenous substrates. These enzymes are also the major ones involved in the oxidation of potential toxicants and carcinogens such as those encountered among pollutants, solvents, and pesticides, as well as many natural products. A proper understanding of the basic mechanisms by which the P450 enzymes oxidize such compounds is important in developing rational strategies for the evaluation of the risks of these compounds.

DNA adduction by the potent carcinogen aflatoxin B1 : mechanistic studies

Aflatoxin B1, a potently carcinogenic fungal metabolite, is converted to the biologically active form by chemical oxidation using dimethyldioxirane and enzymatically by cytochrome P450 mixed-function oxidases. Both processes give rise to mixtures of the exo- and endo-8,9-epoxides. Methanolysis studies reveal exclusive trans opening of both epoxides under neutral conditions in CH3OH and CH3OH/H2O mixtures; an SN2 mechanism is postulated. Under acidic conditions, the exo isomer gives mixtures of trans and cis solvolysis products, suggesting that the reaction is, at least in part, SN1; the endo isomer gives only the trans product. The exo isomer reacts with DNA by attack of the nitrogen atom at the 7 position of guanine on C8 of the epoxide to give the trans adduct; the endo epoxide fails to form an adduct at this or any other site in DNA. The exo isomer is strongly mutagenic in a base-pair reversion assay employing Salmonella typhimurium; the endo isomer is essentially nonmutagenic. Aflatoxin B1 and its derivatives intercalate in DNA. These results are consistent with a mechanism in which intercalation of the exo epoxide optimally orients the epoxide for an SN2 reaction with guanine but intercalation of the endo isomer places the epoxide in an orientation which precludes reaction. Thus, while the exo epoxide is a potent mutagen, the endo epoxide fails to react with DNA.