The mouse model of Chlamydia genital tract infection: a review of infection, disease, immunity and vaccine development

Chlamydia trachomatis is the most common sexually transmitted bacterial infection worldwide. The impact of this pathogen on human reproduction has intensified research efforts to better understand chlamydial infection and pathogenesis. Whilst there are animal models available that mimic the many aspects of human chlamydial infection, the mouse is regarded as the most practical and widely used of the models. Studies in mice have greatly contributed to our understanding of the host-pathogen interaction and provided an excellent medium for evaluating vaccines. Here we explore the advantages and disadvantages of all animal models of chlamydial genital tract infection, with a focus on the murine model and what we have learnt from it so far.

Cadherins in the human placenta : epithelial-mesenchymal transition (EMT) and placental development

Colonisation of the maternal uterine wall by the trophoblast involves a series of alterations in the behaviour and morphology of trophoblast cells. Villous cytotrophoblast cells change from a well-organised coherently layered phenotype to one that is extravillous, acquiring a proliferative, migratory and invasive capacity, to facilitate fetal-maternal interaction. These changes are similar to those of other developmental processes falling under the umbrella of an epithelial-mesenchymal transition (EMT). Modulation of cell adhesion and cell polarity occurs through changes in cell-cell junctional molecules, such as the cadherins. The cadherins, particularly the classical cadherins (e.g. Epithelial-(E)-cadherin), and their link to adaptors called catenins at cell-cell contacts, are important for maintaining cell attachment and the layered phenotype of the villous cytotrophoblast. In contrast, reduced expression and re-organization of cadherins from these cell junctional regions promote a loosened connection between cells, coupled with reduced apico-basal polarity. Certain non-classical cadherins play an active role in cell migration processes. In addition to the classical cadherins, two other cadherins which have been reported in placental tissues are vascular endothelial (VE) cadherin and cadherin-11. Cadherin molecules are well placed to be key regulators of trophoblast cell behaviour, analogous to their role in other developmental EMTs. This review addresses cadherin expression and function in normal and diseased human placental tissues, especially in fetal growth restriction and pre-eclampsia where trophoblast invasion is reduced.

Art spaces in community and economic development : connections to neighborhoods, artists, and the cultural economy

There is growing interest in the arts in community and economic development, yet little research examines the dynamics of community-based arts institutions to inform urban planning and policy. Drawing on interviews with participants and organizers of small and midsized art spaces, the study explores the factors that influence their involvement in neighborhood revitalization and outreach, support for artistic communities, and efforts to build bridges to commercial cultural sectors. Art spaces function as a conduit for building social networks that contribute to both community revitalization and artistic development. But issues pertaining to the location, organization, and management of art spaces may limit their community and economic development potential. The article concludes with proposals to craft stronger arts-based community and economic development programs.

Assessment of damages for defamation of business and personal reputation

An award of damages for defamation is to provide reparation for harm to a plaintiff’s reputation for the publication of defamatory material, compensate for any personal distress caused and vindicate the plaintiff’s reputation.1 Assessing such damages is recognised as a difficult task and perhaps the Queensland courts face further difficulties as there are few awards of damages for defamation in the state. This was pointed out in the recent decision of the Queensland Court of Appeal, Cerutti & Anor v Crestside Pty Ltd & Anor.2 This decision examined in detail the principles of assessing damages for defamation.

A story about being engaged in research : buzzing bees, small business and Australian unfair dismissal laws

Protection for employees from unfair dismissal (UFD) has been around in Australia under various guises for 30 years or so (Chapman, 2006). Labour standards, and particularly ILO Convention 158 (Convention Concerning Termination of Employment at the Initiative of the Employer 1982), underpin the adoption of a particular form of federal statutory UFD regime which first appeared in the 1993 reforms to the Industrial Relations Act 1998 (Commonwealth). Its existence, however, has not been uncontroversial, and the meaning, operation, scope and remedies have attracted attention over time. In fact, the first reforms to the federal UFD regime were undertaken under the Keating Labor government three months after they were enacted (Chapman, ibid.). Further reforms were made by the incoming Howard Liberal-national coalition government through the Workplace Relations Act 1996 (Commonwealth) (WRA), and arguably these reforms continued down the ‘contraction’ path (ibid.).

Protection of intellectual property in Islamic Shari'a and the development of the Libyan intellectual property system

This thesis introduces a theory of intellectual property (IP) law informed by Islamic Shari'a. The sources and objectives of Islamic Shari'a support the theoretical framework underpinning IP laws. However, they strongly emphasise the importance of development goals in intellectual property policy making. This thesis argues that an optimal IP system from an Islamic perspective shall not overprotect IP holders but should instead endeavor to empower people to access knowledge resources to enhance access to education, public health and economic opportunities. Taking Libya as a case study, this thesis makes recommendations for the improvement of IP law that have important broader implications for developing countries.

Enhancing social work interprofessional learning through across university and industry collaboration : early steps in the Advanced Health Directives Project

There is ongoing interest in strategies for enhancing the reciprocal benefit derived from social work placements by students, host agencies, and universities. There is also recognition that interprofessional learning is an important aspect of social work education,and that field education placements have a role to play in this learning. This article reports on an innovation in community-engaged learning undertaken between a major public hospital and a university, where a team of social work and law students contributed to a focused inquiry into a socio-legal practice challenge faced by the hospital, namely the use of Advanced Health Directives (AHDs).Various collaborative processes involved in the early phase of the AHD project are reflected on by participants.A preliminary evaluation supports the value of taking a systematic approach to university–industry engagement where interprofessional collaboration occurs vertically and horizontally within and across university and placement hosting agencies.

The United Nations Guiding Principles on Business and Human Rights : Putting Accounting for Human Rights into Practice

The “Guiding Principles on Business and Human Rights: Implementing the United Nations ‘Protect, Respect and Remedy Framework’” (the Guiding Principles), endorsed by The United Nations Human Rights Council on 16 June 2011, outline obligations for nation states that currently exist under international law and provide the first authoritative reference point for corporations’ human rights responsibilities. Of the 30 principles endorsed, half relate directly to business. The Guiding Principles have far-reaching implications for all businesses, both small and large, and represent one of the most significant developments in corporate governance this century. In response to a recognition of the potential impacts of the Guiding Principles on corporate governance, the Institute of Chartered Accountants in Australia provided La Trobe Business School with grant funding to undertake groundbreaking research on the implications of the Guiding Principles for management and accounting systems within corporate Australia. This report represents the outcome of the study.

Cord blood vitamin D and neurocognitive development are nonlinearly related in toddlers

Background Little is known about the relation between vitamin D status in early life and neurodevelopment outcomes. Objective This study was designed to examine the association of cord blood 25-hydroxyvitamin D [25(OH)D] at birth with neurocognitive development in toddlers. Methods As part of the China-Anhui Birth Cohort Study, 363 mother-infant pairs with completed data were selected. Concentrations of 25(OH)D in cord blood were measured by radioimmunoassay. Mental development index (MDI) and psychomotor development index (PDI) in toddlers were assessed at age 16–18 mo by using the Bayley Scales of Infant Development. The data on maternal sociodemographic characteristics and other confounding factors were also prospectively collected. Results Toddlers in the lowest quintile of cord blood 25(OH)D exhibited a deficit of 7.60 (95% CI: −12.4, −2.82; P = 0.002) and 8.04 (95% CI: −12.9, −3.11; P = 0.001) points in the MDI and PDI scores, respectively, compared with the reference category. Unexpectedly, toddlers in the highest quintile of cord blood 25(OH)D also had a significant deficit of 12.3 (95% CI: −17.9, −6.67; P < 0.001) points in PDI scores compared with the reference category. Conclusions This prospective study suggested that there was an inverted-U–shaped relation between neonatal vitamin D status and neurocognitive development in toddlers. Additional studies on the optimal 25(OH)D concentrations in early life are needed.

Engineering education and sustainable development: Rapid curriculum renewal

The issue of engineering education and how it can systemically embed sustainable development knowledge and skills is now a major consideration for engineering educators globally. In this plenary presentation Ms Desha will begin by highlighting the rapidly changing market and regulatory environment and the time lag dilemma facing higher education with regard to delivering professionals who can address societal needs. She will then briefly present a series of elements of curriculum renewal to support engineering educators who are grappling with how programs of study can be rapidly renewed to address such emerging 21st Century challenges. The presentation will conclude with a discussion of the need for astrategic approach by higher education institutions, to ensure that the latest research and opportunities are communicated, while being sufficiently pragmatic and realistic with regard to the scale of the challenges, and existing inertia within the higher education system.

Targeting ASCT2-mediated glutamine uptake blocks prostate cancer growth and tumour development

Glutamine is conditionally essential in cancer cells, being utilized as a carbon and nitrogen source for macromolecule production, as well as for anaplerotic reactions fuelling the tricarboxylic acid (TCA) cycle. In this study, we demonstrated that the glutamine transporter ASCT2 (SLC1A5) is highly expressed in prostate cancer patient samples. Using LNCaP and PC-3 prostate cancer cell lines, we showed that chemical or shRNA-mediated inhibition of ASCT2 function in vitro decreases glutamine uptake, cell cycle progression through E2F transcription factors, mTORC1 pathway activation and cell growth. Chemical inhibition also reduces basal oxygen consumption and fatty acid synthesis, showing that downstream metabolic function is reliant on ASCT2-mediated glutamine uptake. Furthermore, shRNA knockdown of ASCT2 in PC-3 cell xenografts significantly inhibits tumour growth and metastasis in vivo, associated with the down-regulation of E2F cell cycle pathway proteins. In conclusion, ASCT2-mediated glutamine uptake is essential for multiple pathways regulating the cell cycle and cell growth, and is therefore a putative therapeutic target in prostate cancer.

Interleukin-23 mediates the intestinal response to microbial β-1,3-glucan and the development of spondyloarthritis pathology in SKG mice

Objective Spondyloarthritides (SpA) occur in 1% of the population and include ankylosing spondylitis (AS) and arthropathy of inflammatory bowel disease (IBD), with characteristic spondylitis, arthritis, enthesitis, and IBD. Genetic studies implicate interleukin-23 (IL-23) receptor signaling in the development of SpA and IBD, and IL-23 overexpression in mice is sufficient for enthesitis, driven by entheseal-resident T cells. However, in genetically prone individuals, it is not clear where IL-23 is produced and how it drives the SpA syndrome, including IBD or subclinical gut inflammation of AS. Moreover, it is unclear why specific tissue involvement varies between patients with SpA. We undertook this study to determine the location of IL-23 production and its role in SpA pathogenesis in BALB/c ZAP-70W163C-mutant (SKG) mice injected intraperitoneally with β-1,3-glucan (curdlan). Methods Eight weeks after curdlan injection in wild-type or IL-17A-/- SKG or BALB/c mice, pathology was scored in tissue sections. Mice were treated with anti-IL-23 or anti-IL-22. Cytokine production and endoplasmic reticulum (ER) stress were determined in affected organs. Results In curdlan-treated SKG mice, arthritis, enthesitis, and ileitis were IL-23 dependent. Enthesitis was specifically dependent on IL-17A and IL-22. IL-23 was induced in the ileum, where it amplified ER stress, goblet cell dysfunction, and proinflammatory cytokine production. IL-17A was pathogenic, while IL-22 was protective against ileitis. IL-22+CD3- innate-like cells were increased in lamina propria mononuclear cells of ileitis-resistant BALB/c mice, which developed ileitis after curdlan injection and anti-IL-22. Conclusion In response to systemic β-1,3-glucan, intestinal IL-23 provokes local mucosal dysregulation and cytokines driving the SpA syndrome, including IL-17/IL-22-dependent enthesitis. Innate IL-22 production promotes ileal tolerance.

Mathematical modeling for improved greenhouse gas balances, agro-ecosystems, and policy development: Lessons from the Australian experience

If the land sector is to make significant contributions to mitigating anthropogenic greenhouse gas (GHG) emissions in coming decades, it must do so while concurrently expanding production of food and fiber. In our view, mathematical modeling will be required to provide scientific guidance to meet this challenge. In order to be useful in GHG mitigation policy measures, models must simultaneously meet scientific, software engineering, and human capacity requirements. They can be used to understand GHG fluxes, to evaluate proposed GHG mitigation actions, and to predict and monitor the effects of specific actions; the latter applications require a change in mindset that has parallels with the shift from research modeling to decision support. We compare and contrast 6 agro-ecosystem models (FullCAM, DayCent, DNDC, APSIM, WNMM, and AgMod), chosen because they are used in Australian agriculture and forestry. Underlying structural similarities in the representations of carbon flows though plants and soils in these models are complemented by a diverse range of emphases and approaches to the subprocesses within the agro-ecosystem. None of these agro-ecosystem models handles all land sector GHG fluxes, and considerable model-based uncertainty exists for soil C fluxes and enteric methane emissions. The models also show diverse approaches to the initialisation of model simulations, software implementation, distribution, licensing, and software quality assurance; each of these will differentially affect their usefulness for policy-driven GHG mitigation prediction and monitoring. Specific requirements imposed on the use of models by Australian mitigation policy settings are discussed, and areas for further scientific development of agro-ecosystem models for use in GHG mitigation policy are proposed.

Proteogenomics of selective susceptibility to endotoxin using circulating acute phase biomarkers and bioassay development in sheep: a review

Scientists have injected endotoxin into animals to investigate and understand various pathologies and novel therapies for several decades. Recent observations have shown that there is selective susceptibility to Escherichia coli lipopolysaccharide (LPS) endotoxin in sheep, despite having similar breed characteristics. The reason behind this difference is unknown, and has prompted studies aiming to explain the variation by proteogenomic characterisation of circulating acute phase biomarkers. It is hypothesised that genetic trait, biochemical, immunological and inflammation marker patterns contribute in defining and predicting mammalian response to LPS. This review discusses the effects of endotoxin and host responses, genetic basis of innate defences, activation of the acute phase response (APR) following experimental LPS challenge, and the current approaches employed in detecting novel biomarkers including acute phase proteins (APP) and micro-ribonucleic acids (miRNAs) in serum or plasma. miRNAs are novel targets for elucidating molecular mechanisms of disease because of their differential expression during pathological, and in healthy states. Changes in miRNA profiles during a disease challenge may be reflected in plasma. Studies show that gel-based two-dimensional electrophoresis (2-DE) coupled with either matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) or liquid chromatography-mass spectrometry (LC-MS/MS) are currently the most used methods for proteome characterisation. Further evidence suggests that proteomic investigations are preferentially shifting from 2-DE to non-gel based LC-MS/MS coupled with data extraction by sequential window acquisition of all theoretical fragment-ion spectra (SWATH) approaches that are able to identify a wider range of proteins. Enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), and most recently proteomic methods have been used to quantify low abundance proteins such as cytokines. qRT-PCR and next generation sequencing (NGS) are used for the characterisation of miRNA. Proteogenomic approaches for detecting APP and novel miRNA profiling are essential in understanding the selective resistance to endotoxin in sheep. The results of these methods could help in understanding similar pathology in humans. It might also be helpful in the development of physiological and diagnostic screening assays for determining experimental inclusion and endpoints, and in clinical trials in future