One year on : the devastating Queensland floods

"Tomorrow will mark the one year anniversary of the devastating floods that hit Queensland's Lockyer Valley and Toowoomba and starting today, we'll begin a series of interviews with survivors of those floods on the 10th of January last year. In today's program, Murphy's Creek resident Nelly Gitsham how she sent her family to safety and then ventured into the flood to try to save her neighbour's horse, only to find herself needing to be rescued by another neighbour, John Taylor." Reporter: Amanda Gearing

Demonstration of regulatory cross-talk between P fimbriae and type 1 fimbriae in uropathogenic Escherichia coli

The majority of Escherichia coli strains isolated from urinary tract infections have the potential to express multiple fimbriae. Two of the most common fimbrial adhesins are type 1 fimbriae and pyelonephritis-associated pili (Pap). Previous research has shown that induced, plasmid-based expression of a Pap regulator, papB, and its close homologues can prevent inversion of the fim switch controlling the expression of type 1 fimbriae. The aim of the present study was to determine if this cross-regulation occurs when PapB is expressed from its native promoter in the chromosome of E. coli K-12 and clinical isolates. The regulation was examined in three ways: (1) mutated alleles of the pap regulatory region, including papB and papI, that maintain the pap promoter in either the off or the on phase were exchanged into the chromosome of both E. coli K-12 and the clinical isolate E. coli CFT073, and the effect on type 1 fimbrial expression was measured; (2) type 1 fimbrial expression was determined using a novel fimS : : gfp+ reporter system in mutants of the clinical isolate E. coli 536 in which combinations of complete fimbrial clusters had been deleted; (3) type 1 fimbrial expression was determined in a range of clinical isolates and compared with both the number of P clusters and their expression. All three approaches demonstrated that P expression represses type 1 fimbrial expression. Using a number of novel genetic approaches, this work extends the initial finding that PapB inhibits FimB recombination to the impact of this regulation in clinical isolates.

Whole-genome multiparametric screening to identify modulators of epithelial-to-mesenchymal transition

Metastasis accounts for the poor prognosis of the majority of solid tumors. The phenotypic transition of nonmotile epithelial tumor cells to migratory and invasive “mesenchymal” cells (epithelial-to-mesenchymal transition [EMT]) enables the transit of cancer cells from the primary tumor to distant sites. There is no single marker of EMT; rather, multiple measures are required to define cell state. Thus, the multiparametric capability of high-content screening is ideally suited for the comprehensive analysis of EMT regulators. The aim of this study was to generate a platform to systematically identify functional modulators of tumor cell plasticity using the bladder cancer cell line TSU-Pr1-B1 as a model system. A platform enabling the quantification of key EMT characteristics, cell morphology and mesenchymal intermediate filament vimentin, was developed using the fluorescent whole-cell-tracking reagent CMFDA and a fluorescent promoter reporter construct, respectively. The functional effect of genome-wide modulation of protein-coding genes and miRNAs coupled with those of a collection of small-molecule kinase inhibitors on EMT was assessed using the Target Activation Bioapplication integrated in the Cellomics ArrayScan platform. Data from each of the three screens were integrated to identify a cohort of targets that were subsequently examined in a validation assay using siRNA duplexes. Identification of established regulators of EMT supports the utility of this screening approach and indicated capacity to identify novel regulators of this plasticity program. Pathway analysis coupled with interrogation of cancer-related expression profile databases and other EMT-related screens provided key evidence to prioritize further experimental investigation into the molecular regulators of EMT in cancer cells.

Olfactomedin-4 regulation by estrogen in the human endometrium requires epidermal growth factor signaling

Olfactomedin-4 (OLFM-4) is an extracellular matrix protein that is highly expressed in human endometrium. We have examined the regulation and function of OLFM-4 in normal endometrium and in cases of endometriosis and endometrial cancer. OLFM-4 expression levels are highest in proliferative-phase endometrium, and 17 beta-estradiol up-regulates OLFM-4 mRNA in endometrial explant cultures. Using the luciferase reporter under control of the OLFM-4 promoter, it was shown that both 17 beta-estradiol and OH-tamoxifen induce luciferase activity, and epidermal growth factor receptor-1 is required for this estrogenic response. In turn, EGF activates the OLFM-4 promoter, and estrogen receptor-alpha is needed for the complete EGF response. The cellular functions of OLFM-4 were examined by its expression in OLFM-4-negative HEK-293 cells, which resulted in decreased vimentin expression and cell adherence as well as increased apoptosis resistance. In cases of endometriosis and endometrial cancer, OLFM-4 expression correlated with the presence of epidermal growth factor receptor-1 and estrogen receptor-alpha (or estrogen signaling). An increase of OLFM-4 mRNA was observed in the endometrium of endometriosis patients. No change in OLFM-4 expression levels were observed in patients with endometrial cancer relative with controts. In conclusion, cross-talk between estrogen and EGF signaling regulates OLFM-4 expression. The role of OLFM-4 in endometrial tissue remodeling before the secretory phase and during the predisposition and early events in endometriosis can be postulated but requires additional investigation. (Am J Pathol 2010, 177:2495-2508: DOI: 10.2353/ajpath.2010.100026

Detection of DNA mutations using novel SERS (Surface-Enhanced Raman Spectroscopy) diagnostic platform

This article describes the detection of DNA mutations using novel Au-Ag coated GaN substrate as SERS (surface-enhanced Raman spectroscopy) diagnostic platform. Oligonucleotide sequences corresponding to the BCR-ABL (breakpoint cluster region-Abelson) gene responsible for development of chronic myelogenous leukemia were used as a model system to demonstrate the discrimination between the wild type and Met244Val mutations. The thiolated ssDNA (single-strand DNA) was immobilized on the SERS-active surface and then hybridized to a labeled target sequence from solution. An intense SERS signal of the reporter molecule MGITC was detected from the complementary target due to formation of double helix. The SERS signal was either not observed, or decreased dramatically for a negative control sample consisting of labeled DNA that was not complementary to the DNA probe. The results indicate that our SERS substrate offers an opportunity for the development of novel diagnostic assays.

Global journalism investigations in the digital age: Connections and collaborations

Investigative journalists who join what theorist Manuel Castells describes as the ‘network society’ can locate potential news sources using various social media platforms and interview them using Web-based communication technologies. The potential for journalistic investigations involving multi-directional conversations with news sources across the globe is beginning to be explored. Potential news sources who are part of the network society have unprecedented access to specialist investigative reporters irrespective of their location and can speak to them more cost effectively than in the past. This paper explores how new journalism technologies are allowing journalists to call powerful individuals and institutions to account, irrespective of national borders; and how previously silenced individuals are being given a voice. To read an example of international investigative journalism facilitated by a combination of social media, Web-based communications, reporter collaboration and news outlet collaborations see http://www.theaustralian.com.au/news/features/churchs-wall-of-silence-on-sexual-abuse/story-e6frg6z6-1226639077238.

Olfactory ensheathing cells are the main phagocytic cells that remove axon debris during early development of the olfactory system

During development of the primary olfactory system, axon targeting is inaccurate and axons inappropriately project within the target layer or overproject into the deeper layers of the olfactory bulb. As a consequence there is considerable apoptosis of primary olfactory neurons during embryonic and postnatal development and axons of the degraded neurons need to be removed. Olfactory ensheathing cells (OECs) are the glia of the primary olfactory nerve and are known to phagocytose axon debris in the adult and postnatal animal. However, it is unclear when phagocytosis by OECs first commences. We investigated the onset of phagocytosis by OECs in the developing mouse olfactory system by utilizing two transgenic reporter lines: OMP-ZsGreen mice which express bright green fluorescent protein in primary olfactory neurons, and S100β-DsRed mice which express red fluorescent protein in OECs. In crosses of these mice, the fate of the degraded axon debris is easily visualized. We found evidence of axon degradation at embryonic day (E)13.5. Phagocytosis of the primary olfactory axon debris by OECs was first detected at E14.5. Phagocytosis of axon debris continued into the postnatal animal during the period when there was extensive mistargeting of olfactory axons. Macrophages were often present in close proximity to OECs but they contributed only a minor role to clearing the axon debris, even after widespread degeneration of olfactory neurons by unilateral bulbectomy and methimazole treatment. These results demonstrate that from early in embryonic development OECs are the primary phagocytic cells of the primary olfactory nerve.

Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk

Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10−14, odds ratio = 0.86, 95% confidence interval = 0.82–0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression.

A fair use project for Australia: Copyright law and creative freedom

This essay provides a critical assessment of the Fair Use Project based at the Stanford Center for Internet and Society. In evaluating the efficacy of the Fair Use Project, it is worthwhile considering the litigation that the group has been involved in, and evaluating its performance. Part 1 outlines the history of the Stanford Center for Internet and Society, and the aims and objectives of the Fair Use Project. Part 2 considers the litigation in Shloss v. Sweeney over a biography concerning Lucia Joyce, the daughter of the avant-garde literary great, James Joyce. Part 3 examines the dispute over the Harry Potter Lexicon. Part 4 looks at the controversy over the Shepard Fairey poster of President Barack Obama, and the resulting debate with Associated Press. Part 5 of the essay considers the intervention of the Fair Use Project as an amicus curiae in the ‘Column case’. Part 6 explores the participation of the Fair Use Project as an amicus curiae in the litigation over 60 Years Later, an unauthorised literary sequel to J.D. Salinger’s The Catcher in the Rye. Part 7 of the essay investigates the role of the Fair Use project in disputes over copyright law and musical works. Part 8 investigates the role of the Fair Use Project as an advocate in disputes over copyright law, fair use, documentary films, and internet videos. The conclusion has main three arguments. First, it contends that Australia should establish a Fair Use Project to support creative artists in litigation over copyright exceptions. Second, it maintains that Australia should adopt a flexible, open-ended defence of fair use, and draw upon the rich jurisprudence in the United States on the fair use doctrine. Finally, this paper argues that support should be given at an international level to the proposal for a Treaty on Access to Knowledge.

The grapes of wrath: The Coonawarra dispute, geographical indications and international trade

The famous wine region of Coonawarra in South Australia has been promoted as ’Australia's other Red Centre', emphasizing its terra rossa soil and its cabernet sauvignon. In his atlas of the wine regions of Australia, John Beeston comments upon the rich and contested history of the region: ’Coonawarra is certainly the most famous cabernet sauvignon region in Australia, and some would argue, the most renowned wine region in Australia per se'. A reporter, Penelope Debelle, captures a sense of the legal conflict over the parameters of the boundaries of Coonawarra: ’Behind the name Coonawarra, an inglorious contest is being waged that pits the romance of South Australia's terra rossa cool-climate wine region against the cold commercial reality of the label.'This Chapter tells the story behind the Coonawarra litigation, addressing the parties to the dispute; the legal and historical context of the case; and the immediate impact case, as well as its lingering significance. It considers the ’Coonawarra' case as, very literally, a landmark in Australian jurisprudence in respect of intellectual property. This chapter engages in the methodology of ’legal storytelling'. In the field of new historicism, the use of anecdotes - petite histoire - has been seen as a useful way of challenging grand historical narratives. Joel Fineman has observed that the anecdote is ’the literary form or genre that uniquely refers to the real.' This chapter has three parts. Part 1 outlines the European Community - Australia Wine Agreement 1994, and the operation of the Australian Wine and Brandy Corporation Act 1980 (Cth). Part 2 considers the various stages of the dispute over the Coonawarra region - moving from the decision of the Geographical Indications Committee, to the ruling of the Administrative Appeals Tribunal; and the conclusive decision of the Full Court of the Federal Court of Australia. Part 3 examines the implications of the Coonawarra litigation for other wine regions of Australia - most notably, the King Valley in Victoria; but also the Hunter Valley in the New South Wales; and the Margaret River in Western Australia. The conclusion considers the ramifications of the European Community-Australia Wine Agreement 2007, which has been initialed by both sides.

Mandatory reporting laws: Their origin, nature, and development over time

Dozens of countries have enacted mandatory reporting laws in various forms to respond to child abuse and neglect. Other countries including England are currently considering whether to introduce them, and if so in what form. It is important for policymakers, practitioners and researchers to understand these laws’ background, nature and purpose. This chapter outlines the origins and provenance of the first mandatory reporting laws; discusses their nature; describes major developments over time; and identifies some major effects and their consequences. It is shown that the laws are a heterogeneous, organic, flexible mechanism enabling social intervention where otherwise such intervention is severely compromised or impossible. Their primary function is to comprise but one aspect of a multifaceted child welfare system by identifying cases of serious maltreatment which would not otherwise come to light: sexual abuse and severe physical abuse are paradigm examples. The essential role of these laws is therefore primarily a tertiary aspect of a public health model, rather than a purely preventative strategy. Mandatory reporting laws are made by each specific jurisdiction according to its preferred design and function within its socio-political system. There is a spectrum of different approaches from which a jurisdiction can choose: they can apply to a broad or a narrow range of reporter groups, a broad or a narrow range of types of maltreatment, and a broad or a narrow range of instances where abuse or neglect occurs.

Harry Potter and the lexicon of doom

In a three day trial in April 2008, the United States District Court for the Southern District of New York considered whether the Harry Potter Lexicon infringed the intellectual property rights of J.K. Rowling and Warner Brothers. The case has attracted great media attention. As John Crace, a reporter for The Guardian, observed: “On one side: global-celebrity author J.K. Rowling. On the other: an amateur fan site devoted to the world's favourite boy wizard. At stake: the soul of Harry Potter.” J.K. Rowling is the author of the seven book Harry Potter series, which tell the story of a young wizard, Harry Potter, and his battles with Voldemort, the Lord of Darkness. As the court papers noted, “The Harry Potter Books are a modern day publishing phenomenon and success story.” Warner Brothers sought and obtained the film rights to the series. The entertainment company has thus far produced five films; a sixth is due in November 2008; and the final instalment is planned. The Harry Potter Lexicon is a reference guide created by Steven Vander Ark, a former grade school teacher. He has organised a large volume of material on the Harry Potter books and the Harry Potter films on a website in an alphabetical listing, from “A-Z”. The founder of RDR Books, Roger Rapoport, approached Ark to publish the Harry Potter Lexicon in a book form. Ark agreed to this request, and provided the publisher with a condensed version of the web-site. After RDR Books announced its intention to publish the reference book, J.K. Rowling and Warner Brothers brought a legal action in the United States District Court for the Southern District of New York, alleging that the publishers of the Harry Potter Lexicon were in breach of various intellectual property rights. A spokesperson for Warner Brothers and J.K. Rowling observed: "A fan’s affectionate enthusiasm should not obscure acts of plagiarism. The publishers knew what they were doing. The problem remains that the Lexicon takes an enormous amount of Ms. Rowling’s work and adds virtually no original commentary of its own. As we’ve said in court, it takes too much and adds too little. Authors have a duty to prevent the exploitation of their works by people who contribute nothing original, creative or interpretive." The litigation involves the intersection of copyright law, trade mark law, and consumer protection law. It has a wider significance because it deals with the protection of authorial rights; the use of literary indexes, supplements and reference guides; and the clash between character merchandising and fan fiction.

Allergen capture by IgE and IgG enhanced cell-binding by allergen multimers: How complex is it?

Allergic diseases are the most common chronic disease of the western world, costing $7.8 billion per year in lost productivity and medical care in Australia alone.1 IgE is central to the immunopathogenesis of allergic diseases and important advances are now being made on multiple fronts of IgE research. In particular, two groups independently invested in the generation of IgE reporter mice to address the vexing question of the route of development of the elusive IgE+ B cell.2, 3 Two new anti-IgE mAb targeting membrane IgE and cell-bound IgE have the potential to deplete the cellular source of IgE.4, 5 These could be candidates for alternative anti-IgE treatment options with advantages over current anti-IgE therapy (OmalizumAb), which depletes free serum IgE. Researchers are still intrigued by the modes of interaction of IgE with allergen, and with both its receptors; the high affinity FcεR1 on mast cells and basophils, and the low affinity, C-type lectin, IgE receptor, CD23,6 on B cells and monocytes (Figure 1a and b). A new approach to the study of the complexity of these interactions was recently reported by Reginald et al.7 on page 167 of this issue.

Visible light enhanced oxidant free dehydrogenation of aromatic alcohols using Au-Pd alloy nanoparticle catalysts

We find that visible light irradiation of gold–palladium alloy nanoparticles supported on photocatalytically inert ZrO2 significantly enhances their catalytic activity for oxidant-free dehydrogenation of aromatic alcohols to the corresponding aldehydes at ambient temperatures. Dehydrogenation is also the dominant process in the selective oxidation of the alcohols to the corresponding aldehydes with molecular oxygen. The alloy nanoparticles strongly absorb light and exhibit superior catalytic and photocatalytic activity when compared to either pure palladium or gold nanoparticles. Analysis with a free electron gas model for the bulk alloy structure reveals that the alloying increases the surface charge heterogeneity on the alloy particle surface, which enhances the interaction between the alcohol molecules and the metal NPs. The increased surface charge heterogeneity of the alloy particles is confirmed with density function theory applied to small alloy clusters. Optimal catalytic activity was observed with a Au : Pd molar ratio of 1 : 186, which is in good agreement with the theoretical analysis. The rate-determining step of the dehydrogenation is hydrogen abstraction. The conduction electrons of the nanoparticles are photo-excited by the incident light giving them the necessary energy to be injected into the adsorbed alcohol molecules, promoting the hydrogen abstraction. The strong chemical adsorption of alcohol molecules facilitates this electron transfer. The results show that the alloy nanoparticles efficiently couple thermal and photonic energy sources to drive the dehydrogenation. These findings provide useful insight into the design of catalysts that utilize light for various organic syntheses at ambient temperatures.

Dynamic, invivo, real-time detection of retinal oxidative status in a model of elevated intraocular pressure using a novel, reversibly responsive, profluorescent nitroxide probe

Changes to the redox status of biological systems have been implicated in the pathogenesis of a wide variety of disorders including cancer, Ischemia-reperfusion (I/R) injury and neurodegeneration. In times of metabolic stress e.g. ischaemia/reperfusion, reactive oxygen species (ROS) production overwhelms the intrinsic antioxidant capacity of the cell, damaging vital cellular components. The ability to quantify ROS changes in vivo, is therefore essential to understanding their biological role. Here we evaluate the suitability of a novel reversible profluorescent probe containing a redox-sensitive nitroxide moiety (methyl ester tetraethylrhodamine nitroxide, ME-TRN), as an in vivo, real-time reporter of retinal oxidative status. The reversible nature of the probe's response offers the unique advantage of being able to monitor redox changes in both oxidizing and reducing directions in real time. After intravitreal administration of the ME-TRN probe, we induced ROS production in rat retina using an established model of complete, acute retinal ischaemia followed by reperfusion. After restoration of blood flow, retinas were imaged using a Micron III rodent fundus fluorescence imaging system, to quantify the redox-response of the probe. Fluorescent intensity declined during the first 60 min of reperfusion. The ROS-induced change in probe fluorescence was ameliorated with the retinal antioxidant, lutein. Fluorescence intensity in non-Ischemia eyes did not change significantly. This new probe and imaging technology provide a reversible and real-time response to oxidative changes and may allow the in vivo testing of antioxidant therapies of potential benefit to a range of diseases linked to oxidative stress