Responding to a transformative stressor : climate change and the institutional governance of Australian cities

This paper understands climate change as a transformative stressor that will prompt responses from institutional governance frameworks in Australian cities. A transformative stressor is characterised as a chronic large-scale phenomenon which triggers a process of institutional change whereby institutions seek to reorientate their activities to better manage the social, economic and environmental impacts created by the transformative dynamic. It is posited that institutional change will be required as Australian metropolitan institutional governance frameworks seek to manage climate change effects in urban environments. It is argued that improved operationalisation of adaptation is required as part of a comprehensive urban response to the transformative stresses climate change and its effects are predicted to create in Australian cities. The operationalisation of adaptation refers to adaptation becoming incorporated, codified and implemented as a central principle of metro-regional planning governance. This paper has three key purposes. First, it examines theoretical and conceptual understandings of the role of transformative stressors in compelling institutional change within urban settings. Second, it establishes a conceptual approach that understands climate change as a transformative stressor requiring institutional change within the metropolitan planning frameworks of Australia's cities. Third, it offers early results and conclusions from an empirical investigation into the current prospects for operationalisation of climate adaptation in planning programs within Southeast Queensland (SEQ) via changes to institutional governance. A significant emerging conclusion is that early climate stresses appear not to be leading to episodic institutional change in the metropolitan planning frameworks of SEQ.

Studies on the pathophysiology and genetic basis of migraine

Migraine is a neurological disorder that affects the central nervous system causing painful attacks of headache. A genetic vulnerability and exposure to environmental triggers can influence the migraine phenotype. Migraine interferes in many facets of people’s daily life including employment commitments and their ability to look after their families resulting in a reduced quality of life. Identification of the biological processes that underlie this relatively common affliction has been difficult because migraine does not have any clearly identifiable pathology or structural lesion detectable by current medical technology. Theories to explain the symptoms of migraine have focused on the physiological mechanisms involved in the various phases of headache and include the vascular and neurogenic theories. In relation to migraine pathophysiology the trigeminovascular system and cortical spreading depression have also been implicated with supporting evidence from imaging studies and animal models. The objective of current research is to better understand the pathways and mechanisms involved in causing pain and headache to be able to target interventions. The genetic component of migraine has been teased apart using linkage studies and both candidate gene and genome-wide association studies, in family and case-control cohorts. Genomic regions that increase individual risk to migraine have been identified in neurological, vascular and hormonal pathways. This review discusses knowledge of the pathophysiology and genetic basis of migraine with the latest scientific evidence from genetic studies.

Analysis of the MTHFR C677T variant with migraine phenotypes

Background The methylenetetrahydrofolate reductase (MTHFR) gene variant C677T has been implicated as a genetic risk factor in migraine susceptibility, particularly in Migraine with Aura. Migraine, with and without aura (MA and MO) have many diagnostic characteristics in common. It is postulated that migraine symptomatic characteristics might themselves be influenced by MTHFR. Here we analysed the clinical profile, migraine symptoms, triggers and treatments of 267 migraineurs previously genotyped for the MTHFR C677T variant. The chi-square test was used to analyse all potential relationships between genotype and migraine clinical variables. Regression analyses were performed to assess the association of C677T with all migraine clinical variables after adjusting for gender. Findings The homozygous TT genotype was significantly associated with MA (P < 0.0001) and unilateral head pain (P = 0.002). While the CT genotype was significantly associated with physical activity discomfort (P < 0.001) and stress as a migraine trigger (P = 0.002). Females with the TT genotype were significantly associated with unilateral head pain (P < 0.001) and females with the CT genotype were significantly associated with nausea (P < 0.001), osmophobia (P = 0.002), and the use of natural remedy for migraine treatment (P = 0.003). Conversely, male migraineurs with the TT genotype experienced higher incidences of bilateral head pain (63% vs 34%) and were less likely to use a natural remedy as a migraine treatment compared to female migraineurs (5% vs 20%). Conclusions MTHFR genotype is associated with specific clinical variables of migraine including unilateral head pain, physical activity discomfort and stress.

Proteolytic activation of Chlamydia trachomatis HTRA is mediated by PDZ1 domain interactions with protease domain loops L3 and LC and beta strand β5

Chlamydia trachomatis is a bacterial pathogen responsible for one of the most prevalent sexually transmitted infections worldwide. Its unique development cycle has limited our understanding of its pathogenic mechanisms. However, CtHtrA has recently been identified as a potential C. trachomatis virulence factor. CtHtrA is a tightly regulated quality control protein with a monomeric structural unit comprised of a chymotrypsin-like protease domain and two PDZ domains. Activation of proteolytic activity relies on the C-terminus of the substrate allosterically binding to the PDZ1 domain, which triggers subsequent conformational change and oligomerization of the protein into 24-mers enabling proteolysis. This activation is mediated by a cascade of precise structural arrangements, but the specific CtHtrA residues and structural elements required to facilitate activation are unknown. Using in vitro analysis guided by homology modeling, we show that the mutation of residues Arg362 and Arg224, predicted to disrupt the interaction between the CtHtrA PDZ1 domain and loop L3, and between loop L3 and loop LD, respectively, are critical for the activation of proteolytic activity. We also demonstrate that mutation to residues Arg299 and Lys160, predicted to disrupt PDZ1 domain interactions with protease loop LC and strand β5, are also able to influence proteolysis, implying their involvement in the CtHtrA mechanism of activation. This is the first investigation of protease loop LC and strand β5 with respect to their potential interactions with the PDZ1 domain. Given their high level of conservation in bacterial HtrA, these structural elements may be equally significant in the activation mechanism of DegP and other HtrA family members.

Organizational reframing : the commercialization of a public sector organization

The purpose of this study is to elaborate shared schema change theory in the context of the radical restructuring-commercialization of an Australian public infrastructure organization. Commercialization of the case organization imposed high individual and collective cognitive processing and emotional demands as organizational members sought to develop new shared schema. Existing schema change research suggests that radical restructuring renders pre-existing shared schema irrelevant and triggers new schema development through experiential learning (Balogun and Johnson, 2004). Focus groups and semi-structured interviews were conducted at four points over a three-year period. The analysis revealed that shared schema change occurred in three broad phases: (1) radical restructuring and aftermath; (2) new CEO and new change process schema, and: (3) large-group meeting and schema change. Key findings include: (1) radical structural change does not necessarily trigger new shared schema development as indicated in prior research; (2) leadership matters, particularly in framing new means-ends schema; (3) how change leader interventions are sequenced has an important influence on shared schema change, and; (4) the creation of facilitated social processes have an important influence on shared schema change.

C. elegans RNA-dependent RNA polymerases rrf-1 and ego-1 silence Drosophila transgenes by differing mechanisms

Drosophila possesses the core gene silencing machinery but, like all insects, lacks the canonical RNA-dependent RNA polymerases (RdRps) that in C. elegans either trigger or enhance two major small RNA-dependent gene silencing pathways. Introduction of two different nematode RdRps into Drosophila showed them to be functional, resulting in differing silencing activities. While RRF-1 enhanced transitive dsRNA-dependent silencing, EGO-1 triggered dsRNA-independent silencing, specifically of transgenes. The strain w; da-Gal4; UAST-ego-1, constitutively expressing ego-1, is capable of silencing transgene including dsRNA hairpin upon a single cross, which created a powerful tool for research in Drosophila. In C. elegans, EGO-1 is involved in transcriptional gene silencing (TGS) of chromosome regions that are unpaired during meiosis. There was no opportunity for meiotic interactions involving EGO-1 in Drosophila that would explain the observed transgene silencing. Transgene DNA is, however, unpaired during the pairing of chromosomes in embryonic mitosis that is an unusual characteristic of Diptera, suggesting that in Drosophila, EGO-1 triggers transcriptional silencing of unpaired DNA during embryonic mitosis. © 2012 Springer Basel.

Footprints to pathways : reconciliation action planning in industry to sustain Indigenous employment in Queensland

This paper provides an introductory discussion to a study focusing on industry Reconciliation Action Plans (RAP) and sustaining Indigenous employment in Queensland. Indigenous people continue to experience deep and persistent disadvantage in employment, which limits their life prospects (McLachlan, Gilgillan & Gordon, 2013). A major contributing factor to this detriment is irregular employment and or unemployment. A reasonable standard of living has been found to be determined by access to economic resources such as income and wealth. Denial of this access, denies access to income streams, social status, and engagement in meaningful activities. Hence, job loss and joblessness are triggers of disadvantage (McLachlan, et al., 2013). For young Indigenous people, lack of access has lasting effects particularly if they have multiple characteristics that place them at risk of disadvantage. The project aims to develop knowledge and understanding of Industry RAPs mediate employment opportunities for Indigenous people and how young Indigenous people conceive of their employment options and the processes by which employers can best support Indigenous people. It adopts two theoretical frameworks to investigate the aim of the study : (1) Lave and Wenger’s (1991) theory of communities of practice and, (2) Sen’s (1993) capability approach which provides a structure for examining individual well-being in the context of societal inequality. This paper discusses the first research question of the study: What are Industry Reconciliation Action Plans? What is included in RAPs? Why do Industries develop RAPs? How do RAPs attract, recruit, retain, and tenure Indigenous people? The project’s significance rests with its focus on Industry, employers, policies and practices that aid the attraction and retention of Indigenous people in employment.

Differential Regulation of Clusterin Isoforms by the Androgen Receptor

Clusterin (CLU) was initially reported as an androgen-repressed gene which is now shown to be an androgen-regulated ATP-independent cytoprotective molecular chaperone. CLU binds to a wide variety of client proteins to potently inhibit stress-induced protein aggregation and chaperone or stabilise conformations of proteins at times of cell stress. CLU is an enigmatic protein, being ascribed both pro- and anti-apoptotic roles. Recent evidence has shown that both secreted (sCLU) and nuclear (nCLU) isoforms can be produced, and that protein function is dependent on the sub-cellular localisation. We and others have shown that sCLU is cytoprotective, while nCLU is pro-apoptotic. It now seems likely that the apparently dichotomous functions of CLU result from the expression of different but related CLU isoforms and splice variants, and that cell survival depends in part on the relative expression of pro- versus anti-apoptotic CLU proteins. In cancer cells, increased sCLU expression is associated with increased resistance to apoptotic triggers and treatment resistance. CLU is a stress-induced protein upregulated after apoptotic triggers like androgen ablation and chemotherapy. Treatment strategies targeting stress-associated increases in sCLU expression enhance treatment-induced apoptosis and delay the emergence of androgen independence. Differential regulation of CLU isoforms and splice variants by androgens may be a pathway whereby cancer cells develop treatment resistance and evade apoptosis.

PTSD and traumatic stress : from gene to community and bench to bedside

Individuals and communities are exposed to traumatic events, those that are accidents or naturally occurring and those that are intentional or human made. Although resilience is the expected response, for some, posttraumatic stress disorder may be the outcome. Brain models of PTSD require understanding the phenomenology of the disorder and the brain “break down” that occurs. Among several models, importantly, is the perspective that PTSD is a “forgetting” disorder. Other elements in the onset and triggers of PTSD can identify further models to examine at the bench. New studies of the 5-HT2A receptor, the glucocorticoid receptor, p11, mitochondrial genes and cannabinoids are bringing new perspectives to understanding brain function in PTSD. Effective treatments indicate areas for bench research on the mechanisms of the disorder.

Numerical simulation of downburst winds

The wind field of an intense idealised downburst wind storm has been studied using an axisymmetric, dry, non-hydrostatic numerical sub-cloud model. The downburst driving processes of evaporation and melting have been paramaterized by an imposed cooling source that triggers and sustains a downdraft. The simulated downburst exhibits many characteristics of observed full-scale downburst events, in particular the presence of a primary and counter rotating secondary ring vortex at the leading edge of the diverging front. The counter-rotating vortex is shown to significantly influence the development and structure of the outflow. Numerical forcing and environmental characteristics have been systematically varied to determine the influence on the outflow wind field. Normalised wind structure at the time of peak outflow intensity was generally shown to remain constant for all simulations. Enveloped velocity profiles considering the velocity structure throughout the entire storm event show much more scatter. Assessing the available kinetic energy within each simulated storm event, it is shown that the simulated downburst wind events had significantly less energy available for loading isolated structures when compared with atmospheric boundary layer winds. The discrepancy is shown to be particularly prevalent when wind speeds were integrated over heights representative of tall buildings. A similar analysis for available full scale measurements led to similar findings.

Breast cancer stem cells and epithelial mesenchymal plasticity : implications for chemoresistance

Tumour heterogeneity is a key characteristic of cancer and has significant implications relating to tumour response to chemotherapy as well as patient prognosis and potential relapse. It is being increasingly accepted that tumours are clonal in origin, suggestive of a tumour arising from a deregulated or mutated cell. Cancer stem cells (CSC) possess these capabilities, and with appropriate intracellular triggers and/or signalling from extracellular environments, can purportedly differentiate to initiate tumour formation. Additionally through epithelial mesenchymal plasticity (EMP), where cells gain and maintain characteristics of both epithelial and mesenchymal cell types, epithelial-derived tumour cells have been shown to de-differentiate to acquire cancer stem attributes, which also impart chemotherapy resistance. This new paradigm places EMP centrally in the process of tumour progression and metastasis, as well as modulating drug response to current forms of chemotherapy. Furthermore, EMP and CSCs have been identified in cancers arising from different tissue types making it a possible generic therapeutic target in cancer biology. Using breast cancer (BrCa) as an example, we summarise here the current understanding of CSCs, the role of EMP in cancer biology - especially in CSCs and different molecular subtypes, and the implications this has for current and future cancer treatment strategies.

The impact of viral respiratory infection on the severity and recovery from an asthma exacerbation

Background Viral respiratory illness triggers asthma exacerbations, but the influence of respiratory illness on the acute severity and recovery of childhood asthma is unknown. Our objective was to evaluate the impact of a concurrent acute respiratory illness (based on a clinical definition and PCR detection of a panel of respiratory viruses, Mycoplasma pneumoniae and Chlamydia pneumoniae) on the severity and resolution of symptoms in children with a nonhospitalized exacerbation of asthma. Methods Subjects were children aged 2 to 15 years presenting to an emergency department for an acute asthma exacerbation and not hospitalized. Acute respiratory illness (ARI) was clinically defined. Nasopharyngeal aspirates (NPA) were examined for respiratory viruses, Chlamydia and Mycoplasma using PCR. The primary outcome was quality of life (QOL) on presentation, day 7 and day 14. Secondary outcomes were acute asthma severity score, asthma diary, and cough diary scores on days 5, 7,10, and 14. Results On multivariate regression, presence of ARI was statistically but not clinically significantly associated with QOL score on presentation (B = 0.36, P = 0.025). By day 7 and 14, there was no difference between groups. Asthma diary score was significantly higher in children with ARI (B = 0.41, P = 0.039) on day 5 but not on presentation or subsequent days. Respiratory viruses were detected in 54% of the 78 NPAs obtained. There was no difference in the any of the asthma outcomes of children grouped by positive or negative NPA. Conclusions The presence of a viral respiratory illness has a modest influence on asthma severity, and does not influence recovery from a nonhospitalized asthma exacerbation.

Coincident sequence-specific RNA degradation of linked transgenes in the plant genome

The expression of transgenes in plant genomes can be inhibited by either transcriptional gene silencing or posttranscriptional gene silencing (PTGS). Overexpression of the chalcone synthase-A (CHS-A) transgene triggers PTGS of CHS-A and thus results in loss of flower pigmentation in petunia. We previously demonstrated that epigenetic inactivation of CHS-A transgene transcription leads to a reversion of the PTGS phenotype. Although neomycin phosphotransferase II (nptII), a marker gene co-introduced into the genome with the CHS-A transgene, is not normally silenced in petunia, even when CHS-A is silenced, here we found that nptII was silenced in a petunia line in which CHS-A PTGS was induced, but not in the revertant plants that had no PTGS of CHS-A. Transcriptional activity, accumulation of short interfering RNAs, and restoration of mRNA level after infection with viruses that had suppressor proteins of gene silencing indicated that the mechanism for nptII silencing was posttranscriptional. Read-through transcripts of the CHS-A gene toward the nptII gene were detected. Deep-sequencing analysis revealed a striking difference between the predominant size class of small RNAs produced from the read-through transcripts (22 nt) and that from the CHS-A RNAs (21 nt). These results implicate the involvement of read-through transcription and distinct phases of RNA degradation in the coincident PTGS of linked transgenes and provide new insights into the destabilization of transgene expression.

When supply does not meet demand-ER stress and plant programmed cell death

The endoplasmic reticulum (ER) is the central organelle in the eukaryotic secretory pathway. The ER functions in protein synthesis and maturation and is crucial for proper maintenance of cellular homeostasis and adaptation to adverse environments. Acting as a cellular sentinel, the ER is exquisitely sensitive to changing environments principally via the ER quality control machinery. When perturbed, ER-stress triggers a tightly regulated and highly conserved, signal transduction pathway known as the unfolded protein response (UPR) that prevents the dangerous accumulation of unfolded/misfolded proteins. In situations where excessive UPR activity surpasses threshold levels, cells deteriorate and eventually trigger programmed cell death (PCD) as a way for the organism to cope with dysfunctional or toxic signals. The programmed cell death that results from excessive ER stress in mammalian systems contributes to several important diseases including hypoxia, neurodegeneration, and diabetes. Importantly, hallmark features and markers of cell death that are associated with ER stress in mammals are also found in plants. In particular, there is a common, conserved set of chaperones that modulate ER cell death signaling. Here we review the elements of plant cell death responses to ER stress and note that an increasing number of plant-pathogen interactions are being identified in which the host ER is targeted by plant pathogens to establish compatibility.

100 futures now : designing sustainable futures

This presentation tells the story of an initiative in middle schooling at Kelvin Grove State College that begins in the Art studios, but reaches out to other disciplines and approaches, and to community and industry partners. It is inspired by the potential of 'future thinking' to become a compelling focus in contemporary art and design. Ethically it espouses a simple premise": every student in our classrooms now has a stake in creating livable, democratic and creative futures. Every student has the potential to be an active force in making that future. "100 Futures Now" is a project that envisages creative and imaginative students working in collaboration with artists and designers to visualize amazing futures and communicate their vision through art and design. "100 Futures Now" is one in a series of innovative curriculum initiatives at Kelvin Grove State College designed to build sustainable practice in arts education with the support of partners in industry and universities and with resident artists and designers. The model blends elements of art and design methodology to focus on the critical and creative thinking skills prioritised in ACARA and 21st century curriculum. The organisers are developing a sustainable model for working with resident artists that goes beyond a single arts intervention or extension/enrichment experience. In this model artists and designers are collaborators in the design of learning experiences that support future programs. This model also looks to transfer the benefits of residencies to the wider school community (in this case to middle schooling curriculum) and to teachers in other curriculum areas, and not exclusively to the immediate target group. In "100 Futures Now", story-making is the engine that powers the creative process. For this reason the program uses a series of imaginative scenarios, including those of speculative fiction and science, as departure points for inquiry, and applies the methodologies of arts and design practice to explore and express student story telling and story making. The story-making responses of student teams will naturally be expressed multimodally through visual art, design artifacts, installation, performance and digital works. The project’s focus on narratives and its modes of communication (performance/installation) are inspired by the work of experimental contemporary design practices and the speculative scenarios of U.K. based designers Anthony Dunne and Fiona Raby. Thanks to the support of an Arts Queensland Artist-in -Residence grant in 2014, resident artists and designers who work with a diversity of ideas and approaches ranging over science, bio-ethics, biodiversity, behavior and ethics, ambient sound, urbanism, food, and wearable design, will work with middle school students as catalysts for deeper thinking and creative action. All these rich fields for future speculation will become triggers for team inquiry into the deeper connections between the past, the present, and future challenges such as climate, waste, energy, sustainability and resilience. These imagined futures will form the platform for a critical, sustainability/design futures approach that will involve questioning assumptions and empowering students as agents rather than consumers of change.