The development of an effective vaccine against Chlamydia : utilisation of a non-toxic mucosal adjuvant to generate a protective mucosal response

Chlamydia is responsible for a wide range of diseases with enormous global economic and health burden. As the majority of chlamydial infections are asymptomatic, a vaccine has greatest potential to reduce infection and disease prevalence. Protective immunity against Chlamydia requires the induction of a mucosal immune response, ideally, at the multiple sites in the body where an infection can be established. Mucosal immunity is most effectively stimulated by targeting vaccination to the epithelium, which is best accomplished by direct vaccine application to mucosal surfaces rather than by injection. The efficacy of needle-free vaccines however is reliant on a powerful adjuvant to overcome mucosal tolerance. As very few adjuvants have proven able to elicit mucosal immunity without harmful side effects, there is a need to develop non-toxic adjuvants or safer ways to administered pre-existing toxic adjuvants. In the present study we investigated the novel non-toxic mucosal adjuvant CTA1-DD. The immunogenicity of CTA1-DD was compared to our "gold-standard" mucosal adjuvant combination of cholera toxin (CT) and cytosine-phosphate-guanosine oligodeoxynucleotide (CpG-ODN). We also utilised different needle-free immunisation routes, intranasal (IN), sublingual (SL) and transcutaneous (TC), to stimulate the induction of immunity at multiple mucosal surfaces in the body where Chlamydia are known to infect. Moreover, administering each adjuvant by different routes may also limit the toxicity of the CT/CpG adjuvant, currently restricted from use in humans. Mice were immunised with either adjuvant together with the chlamydial major outer membrane protein (MOMP) to evaluate vaccine safety and quantify the induction of antigen-specific mucosal immune responses. The level of protection against infection and disease was also assessed in vaccinated animals following a live genital or respiratory tract infectious challenge. The non-toxic CTA1-DD was found to be safe and immunogenic when delivered via the IN route in mice, inducing a comparable mucosal response and level of protective immunity against chlamydial challenge to its toxic CT/CpG counterpart administered by the same route. The utilisation of different routes of immunisation strongly influenced the distribution of antigen-specific responses to distant mucosal surfaces and also abrogated the toxicity of CT/CpG. The CT/CpG-adjuvanted vaccine was safe when administered by the SL and TC routes and conferred partial immunity against infection and pathology in both challenge models. This protection was attributed to the induction of antigen-specific pro-inflammatory cellular responses in the lymph nodes regional to the site of infection and rather than in the spleen. Development of non-toxic adjuvants and effective ways to reduce the side effects of toxic adjuvants has profound implications for vaccine development, particularly against mucosal pathogens like Chlamydia. Interestingly, we also identified two contrasting vaccines in both infection models capable of preventing infection or pathology exclusively. This indicated that the development of pathology following an infection of vaccinated animals was independent of bacterial load and was instead the result of immunopathology, potentially driven by the adaptive immune response generated following immunisation. While both vaccines expressed high levels of interleukin (IL)-17 cytokines, the pathology protected group displayed significantly reduced expression of corresponding IL-17 receptors and hence an inhibition of signalling. This indicated that the balance of IL-17-mediated responses defines the degree of protection against infection and tissue damage generated following vaccination. This study has enabled us to better understand the immune basis of pathology and protection, necessary to design more effective vaccines.

Life Drama : an arts education response to social and cultural challenges in Papua New Guinea

The Life Drama program is a theatre-based experiential learning program developed in Papua New Guinea over the past seven years. The Life Drama team recognises that a significant proportion of “education” for learners of all ages takes place outside formal education systems, particularly in developing nations such as Papua New Guinea. If arts education principles and practices are to contribute meaningfully and powerfully to resolving social and cultural challenges, it is important to recognise that many learners and educators will encounter and use these principles and practices outside of school or university settings. This paper briefly describes the Life Drama program and its context, highlights its two streams of operation (community educators and teacher educators) and indicates some ways in which an arts-based education initiative like Life Drama contributes to Goal 3 of the Seoul Agenda:“Apply arts education principles and practices to contribute to resolving the social and cultural challenges facing today‟s world.” In particular, the project addresses sub-goal 3b:“Recognize and develop the social and cultural well-being dimensions of arts education”.

Dancing Diseases : an applied theatre response to the challenge of conveying emotionally contradictory messages in HIV education

Health educators face an unusual challenge in relation to HIV: the need to convey two emotionally contradictory messages. On the one hand, there is currently no cure for HIV, which eventually leads to death (emotionally negative message). On the other hand, people with HIV can live long, healthy and productive lives (emotionally positive message). In developing countries where HIV prevalence is high, it is imperative that both messages are conveyed effectively. This article reports on a specific form, Dancing Diseases, implemented as one component of the Life Drama pilot study on Karkar Island, Papua New Guinea. Life Drama is an applied theatre and performance approach to HIV education. The article discusses Dancing Diseases as an example of applied theatre and performance practice, reflects on the participant group’s engagement with the form, and offers some ways in which the form could be refined and used in other health education contexts.

Changing work design in disaster response : the potential for innovation

Work design operates as the system of arrangements and procedures for organizing work to achieve organizational goals. These systems are commonly established in periods of environmental and organizational stability and formulated to achieve efficiencies in resources, employee and team configuration. However, organizations charged with responding to disasters need to be prepared to respond to unexpected events on a large scale, and disaster response planning needs to accommodate a broad range of possible disasters. When the disaster state occurs, enactment of the specific organizational response is devolved to group or individual level managers. While this enactment presents a range of risks, it also provides a potential avenue for innovation. Employees ultimately are the foundation of change and innovation, as it is people who develop, respond, change and implement new ideas. This study analyzes motivational characteristics of work design at an Australian humanitarian organization encompassing normal operations and periods of disaster activation. The study will identify the paradox of dual work designs and the implications for organizational innovation.

Molecular characterisation and expression analysis of interferon gamma in response to natural chlamydia infection in the koala, phascolarctos cinereus

Interferon gamma (IFNγ) is a key Th1 cytokine, with a principal role in the immune response against intracellular organisms such as Chlamydia. Along with being responsible for significant morbidity in human populations, Chlamydia is also responsible for wide spread infection and disease in many animal hosts, with reports that many Australian koala subpopulations are endemically infected. An understanding of the role played by IFNγ in koala chlamydial diseases is important for the establishment of better prophylactic and therapeutic approaches against chlamydial infection in this host. A limited number of IFNγ sequences have been published from marsupials and no immune reagents to measure expression have been developed. Through preliminary analysis of the koala transcriptome, we have identified the full coding sequence of the koala IFNγ gene. Transcripts were identified in spleen and lymph node tissue samples. Phylogenetic analysis demonstrated that koala IFNγ is closely related to other marsupial IFNγ sequences and more distantly related to eutherian mammals. To begin to characterise the role of this important cytokine in the koala's response to chlamydial infection, we developed a quantitative real time PCR assay and applied it to a small cohort of koalas with and without active chlamydial disease, revealing significant differences in expression patterns between the groups. Description of the IFNγ sequence from the koala will not only assist in understanding this species' response to its most important pathogen but will also provide further insight into the evolution of the marsupial immune system

Postgraduate response to an information retrieval credit course

Information skills instruction for research candidates bas recently been formalised as coursework at the Queensland University of Technology. Feedback solicited from participants suggests that students benefit from such coursework in a number of ways. Their perception of the value of specific content areas to their literature review and thesis presentation is favourable. A small group of students who participated in Interviews identified five ways in which the coursework assisted the research process. As Instructors continue to work with the post·graduate community it would be useful to deepen our understanding of how such instruction is perceived and the benefits which can be derived from it.

Information skills coursework for postgraduate students : investigation and response at the Queensland University of Technology

In response to current developments In the tertiary education sector, the Queensland University of Technology Library has mounted an Intensive course - Advanced Information Retrieval Skills - for higher degree students. In determining need for such a course, a survey of postgraduate students and their supervisors was conducted. Results of this survey are discussed and details of the four credit point subjects are outlined.

Time and space in biogeography : response to Parenti & Ebach (2013)

A recent Guest Editorial by Parenti & Ebach (2013, Journal of Biogeography, 40, 813–820) disagrees with the methods or interpretations in two of our recent papers. In addition, the authors open a debate on biogeographical concepts, and present an alternative philosophy for biogeographical research in the context of their recently described biogeographical subregion called ‘Pandora’. We disagree with their approach and conclusions, and comment on several issues related to our differing conceptual approaches for biogeographical research; namely, our use of molecular phylogenetic analyses, including time estimates; and Parenti & Ebach's reliance on taxon/general area cladograms. Finally, we re-examine their ‘tests’ supporting the existence of ‘Pandora’.

Shear-critical impact response of biaxially loaded reinforced concrete circular columns

A study on the vulnerability of biaxially loaded reinforced concrete (RC) circular columns in multi-story buildings under low- to medium-velocity impacts at shear-critical locations is presented. The study is based on a previously validated nonlinear explicit dynamic finite element (FE) modeling technique developed by the authors. The impact is simulated using force pulses generated from full-scale vehicle impact tests abundantly found in the literature with a view to quantifying the sensitivity of the design parameters of the RC columns under the typical impacts that are representative of the general vehicle population. The design parameters considered include the diameter and height of the column, the vertical steel ratio, the concrete grade, and the confinement effects. From the results of the simulations, empirical equations to quantify the critical impulses for the simplified design of the short, circular RC columns under the risk of shear-critical impacts are developed.

The effect of MC1R variants and sunscreen on the response of human melanocytes in vivo to ultraviolet radiation and implications for melanoma.

We conducted a clinical trial to compare the molecular and cellular responses of human melanocytes and keratinocytes in vivo to solar-simulated ultraviolet radiation (SSUVR) in 57 Caucasian participants grouped according to MC1R genotype. We found that, on average, the density of epidermal melanocytes 14 days after exposure to 2 minimal erythemal dose (MED) SSUVR was twofold higher than baseline (unirradiated) skin. However, the change in epidermal melanocyte counts among people carrying germline MC1R variants (97% increase) was significantly less than those with wild-type MC1R (164% increase; P = 0.01). We also found that sunscreen applied to the skin before exposure to 2 MED SSUVR completely blocked the effects of DNA damage, p53 induction, and cellular proliferation in both melanocytes and keratinocytes.

Genotypes of the MTHFR C677T and MTRR A66G genes act independently to reduce migraine disability in response to vitamin supplementation

BACKGROUND: Migraine is a chronic disabling neurovascular condition that may in part be caused by endothelial and cerebrovascular disruption induced by hyperhomocysteinaemia. We have previously provided evidence indicating that reduction of homocysteine by vitamin supplementation can reduce the occurrence of migraine in women. The current study examined the genotypic effects of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) gene variants on the occurrence of migraine in response to vitamin supplementation. METHODS: This was a 6-month randomized, double-blinded placebo-controlled trial of daily vitamin B supplementation (B(6), B(9) and B(12)) on reduction of homocysteine and of the occurrence of migraine in 206 female patients diagnosed with migraine with aura. RESULTS: Vitamin supplementation significantly reduced homocysteine levels (P<0.001), severity of headache in migraine (P=0.017) and high migraine disability (P=0.022) in migraineurs compared with the placebo effect (P>0.1). When the vitamin-treated group was stratified by genotype, the C allele carriers of the MTHFR C677T variant showed a higher reduction in homocysteine levels (P<0.001), severity of pain in migraine (P=0.01) and percentage of high migraine disability (P=0.009) compared with those with the TT genotypes. Similarly, the A allele carriers of the MTRR A66G variants showed a higher level of reduction in homocysteine levels (P<0.001), severity of pain in migraine (P=0.002) and percentage of high migraine disability (P=0.006) compared with those with the GG genotypes. Genotypic analysis for both genes combined indicated that the treatment effect modification of the MTRR variant was independent of the MTHFR variant. CONCLUSION: This provided further evidence that vitamin supplementation is effective in reducing migraine and also that both MTHFR and MTRR gene variants are acting independently to influence treatment response in female migraineurs.

Evolution of lure response in tephritid fruit flies : phytochemicals as drivers of sexual selection

The males of many Bactrocera species (Diptera: Tephritidae) respond strongly and positively to a small number of plant-derived chemicals (=male lures). Males that have imbibed the lures commonly have a mating advantage over unfed males, but no female benefits have been demonstrated for females mating with lure-fed males. It has been hypothesized that the strong lure response is a case of runaway selection, where males receive direct benefits and females receive indirect benefits via 'sexy sons', or a case of sensory bias where females have a lower threshold response to lures. To test these hypotheses we studied the effects of lure feeding on male mating, remating and longevity; while for females that had mated with lure-fed males we recorded mating refractoriness, fecundity, egg viability and longevity. We used Bactrocera tryoni as our test animal and as lures the naturally occurring zingerone and chemically related, but synthetic chemical cuelure. Feeding on lures provided direct male benefits in greater mating success and increased multiple mating. For the first time, we recorded direct female effects: increased fecundity and reduced remating receptivity. Egg viability did not differ in females mated with lure-fed or unfed males. The life span of males and females exposed to lures was reduced. These results reveal direct, current-generation fitness benefits for both males and females, although the male benefits appear greater. We discuss that while lure response is indeed likely to be a sexual selection trait, there is no need to invoke runaway selection to explain its evolution.

Genetic response to combined family selection for improved mean harvest weight in giant freshwater prawn (Macrobrachium rosenbergii) in Vietnam

We estimated genetic changes in body and carcass weight traits in a giant freshwater prawn (GFP) (Macrobrachium rosenbergii) population selected for increased body weight at harvest in Vietnam. The data set consisted of 18,387 individual body and 1730 carcass weight records, as well as full pedigree information collected over four generations. Average selection response (per generation) in body weight at harvest (transformed to square root) estimated as the difference between the Selection line and the Control group was 7.4% calculated from least squares mean (LSMs), 7.0% from estimated breeding values (EBVs) and 4.4% calculated from EBVs between two consecutive generations. Favorable correlated selection responses (estimated from LSMs) were found for other body traits including: total length, cephalothorax length, abdominal length, cephalothorax width, and abdominal width (12.1%, 14.5%, 10.4%, 15.5% and 13.3% over three selection generations, respectively). Data in the second generation of selection showed positive correlated responses for carcass weight traits including: abdominal weight, exoskeleton-off weight, and telson-off weight of 8.8%, 8.6% and 8.8%, respectively. We conclude that body weight at harvest responded well to the application of combined (between and within) family selection and correlated responses in carcass weight traits were favorable.