Comparison of cervical and blood T-cell responses to human papillomavirus-16 in women with human papillomavirus-associated cervical intraepithelial neoplasia

Human papillomaviruses (HPVs) are obligate epithelial pathogens and typically cause localized mucosal infections. We therefore hypothesized that T-cell responses to HPV antigens would be greater at sites of pathology than in the blood. Focusing on HPV-16 because of its association with cervical cancer, the magnitude of HPV-specific T-cell responses at the cervix was compared with those in the peripheral blood by intracellular cytokine staining following direct ex vivo stimulation with both virus-like particles assembled from the major capsid protein L1, and the major HPV oncoprotein, E7. We show that both CD4 + and CD8 + T cells from the cervix responded to the HPV-16 antigens and that interferon-γ (IFN-γ) production was HPV type-specific. Comparing HPV-specific T-cell IFN-γ responses at the cervix with those in the blood, we found that while CD4 + and CD8 + T-cell responses to L1 were significantly correlated between compartments (P = 0.02 and P = 0.05, respectively), IFN-γ responses in both T-cell subsets were significantly greater in magnitude at the cervix than in peripheral blood (P = 0.02 and P = 0.003, respectively). In contrast, both CD4 + and CD8 + T-cell IFN-γ responses to E7 were of similar magnitude in both compartments and CD8 + responses were significantly correlated between these distinct immunological compartments (P = 0.04). We therefore show that inflammatory T-cell responses against L1 (but not E7) demonstrate clear compartmental bias and the magnitude of these responses do reflect local viral replication but that correlation of HPV-specific responses between compartments indicates their linkage.

A prime-boost immunisation regimen using recombinant BCG and Pr55 gag virus-like particle vaccines based on HIV type 1 subtype C successfully elicits Gag-specific responses in baboons

Mycobacterium bovis BCG is considered an attractive live bacterial vaccine vector. In this study, we investigated the immune response of baboons to a primary vaccination with recombinant BCG (rBCG) constructs expressing the gag gene from a South African HIV-1 subtype C isolate, and a boost with HIV-1 subtype C Pr55 gag virus-like particles (Gag VLPs). Using an interferon enzyme-linked immunospot assay, we show that although these rBCG induced only a weak or an undetectable HIV-1 Gag-specific response on their own, they efficiently primed for a Gag VLP boost, which strengthened and broadened the immune responses. These responses were predominantly CD8+ T cell-mediated and recognised similar epitopes as those targeted by humans with early HIV-1 subtype C infection. In addition, a Gag-specific humoral response was elicited. These data support the development of HIV-1 vaccines based on rBCG and Pr55 gag VLPs. © 2009 Elsevier Ltd. All rights reserved.

HIV-1 sub-type C chimaeric VLPs boost cellular immune responses in mice

Several approaches have been explored to eradicate HIV; however, a multigene vaccine appears to be the best option, given their proven potential to elicit broad, effective responses in animal models. The Pr55 Gagprotein is an excellent vaccine candidate in its own right, given that it can assemble into large, enveloped, virus-like particles (VLPs) which are highly immunogenic, and can moreover be used as a scaffold for the presentation of other large non-structural HIV antigens. In this study, we evaluated the potential of two novel chimaeric HIV-1 Pr55 Gag-based VLP constructs - C-terminal fusions with reverse transcriptase and a Tat::Nef fusion protein, designated GagRT and GagTN respectively - to enhance a cellular response in mice when used as boost components in two types of heterologous prime-boost vaccine strategies. A vaccine regimen consisting of a DNA prime and chimaeric HIV-1 VLP boosts in mice induced strong, broad cellular immune responses at an optimum dose of 100 ng VLPs. The enhanced cellular responses induced by the DNA prime-VLP boost were two- to three-fold greater than two DNA vaccinations. Moreover, a mixture of GagRT and GagTN VLPs also boosted antigen-specific CD8+ and CD4+ T-cell responses, while VLP vaccinations only induced predominantly robust Gag CD4+ T-cell responses. The results demonstrate the promising potential of these chimaeric VLPs as vaccine candidates against HIV-1. © 2010 Pillay et al; licensee BioMed Central Ltd.

Physiological, perceptual and technical responses to on-court tennis training on hard and clay courts

The aim of this study was to investigate the effect of court surface (clay v hard-court) on technical, physiological and perceptual responses to on-court training. Four high-performance junior male players performed two identical training sessions on hard and clay courts, respectively. Sessions included both physical conditioning and technical elements as led by the coach. Each session was filmed for later notational analysis of stroke count and error rates. Further, players wore a global positioning satellite device to measure distance covered during each session; whilst heart rate, countermovement jump distance and capillary blood measures of metabolites were measured before, during and following each session. Additionally a respective coach and athlete rating of perceived exertion (RPE) were measured following each session. Total duration and distance covered during of each session were comparable (P>0.05; d<0.20). While forehand and backhands stroke volume did not differ between sessions (P>0.05; d<0.30); large effects for increased unforced and forced errors were present on the hard court (P>0.05; d>0.90). Furthermore, large effects for increased heart rate, blood lactate and RPE values were evident on clay compared to hard courts (P>0.05; d>0.90). Additionally, while player and coach RPE on hard courts were similar, there were large effects for coaches to underrate the RPE of players on clay courts (P>0.05; d>0.90). In conclusion, training on clay courts results in trends for increased heart rate, lactate and RPE values, suggesting sessions on clay tend towards higher physiological and perceptual loads than hard courts. Further, coaches appear effective at rating player RPE on hard courts, but may underrate the perceived exertion of sessions on clay courts.

The Australian built environment : current challenges and innovative responses

The exploratory research presented in this discussion paper was undertaken as input to a major research grant application for the Australian Research Council. The research looks at the contribution of the Australian built environment to meet social and environmental needs. The paper examines the following research questions: What are the main challenges facing the Australian built environment? What types of building innovations might address those challenges? The research questions were addressed through desk-top research, involving an international review of (1) relevant academic literature in top-tier construction management and general management journals, and (2) high profile industry reports published internationally. Future research will involve assessing the diffusion of the identified building innovations and gauging their impact on social and environmental goals.

A critical appraisal of responses to Maori offending

This article critically analyses the role that criminological theory and specific policy formulations of culture play in the New Zealand state’s response to the over-representation of Māori in the criminal justice system. Part one provides an overview of the changing criminological explanations of, and responses to, Māori offending in New Zealand from the 1980s onwards and how these understandings extended colonialist approaches to Māori and crime into the neo-colonial context. In particular, we chart the shift in policy development from theorising Māori offending as attributable to loss of cultural identity to a focus on socio-economic and institutional antecedents and, finally, through the risk factors, assessment, and criminogenic needs approaches that have gained prominence in the current policy context. In part two, the focus moves to the strategies employed by members of the academy to elevate their own epistemological constructions of Māori social reality within the policy development process. In particular, the critique scrutinises recent attempts to portray Indigenous responses to social harm as “unscientific” and, in part, responsible for the continuing over-representation of Māori in New Zealand’s criminal justice system. The purpose of this analysis is to focus the critical, criminological gaze firmly on the activities of policy makers and administrative criminologists, to examine how their policies and approaches impact on Māori as an Indigenous people.

Bushfire responsive design : real life responses to energy ratings, bushfire standards and biodiverse sites.

Many of the more extreme bushfire prone landscapes in Australia are located in colder climate regions. For such sites, the National Construction Code regulates that houses satisfy both the Australian Standard for Bushfire (AS 3959:2009) and achieve a 6 Star energy rating. When combined these requirements present a considerable challenge to the construction of affordable housing - a problem which is often exacerbated by the complex topography of bushifre prone landscapes. Dr Weir presents a series of case studies from his architetcural practice which highlight the need for further design-led research into affordable housing - a ground up holistic approach to design which recolciles energy performance, human behaviourm, bushland conservation and bushfire safety.

Carbohydrate gel ingestion and immunoendocrine responses to cycling in temperate and hot conditions

PURPOSE: Heat stress might attenuate the effects of carbohydrate on immunoendocrine responses to exercise by increasing endogenous glucose production and reducing the rate of exogenous carbohydrate oxidation. The authors compared the efficacy of carbohydrate consumption on immune responses to exercise in temperate vs. hot conditions. METHODS: Ten male cyclists exercised on 2 separate occasions in temperate (18.1 +/- 0.4 degrees C, 58% +/- 8% relative humidity) and on another 2 occasions in hot conditions (32.2 +/- 0.7 degrees C, 55% +/- 2% relative humidity). On each occasion, the cyclists exercised in a fed state for 90 min at approximately 60% VO2max and then completed a 16.1-km time trial. Every 15 min during the first 90 min of exercise, they consumed 0.24 g/kg body mass of a carbohydrate or placebo gel. RESULTS: Neutrophil counts increased during exercise in all trials (p < .05) and were significantly lower (40%, p = .006) after the carbohydrate than after the placebo trial in 32 degrees C. The concentrations of serum interleukin (IL)-6, IL-8, and IL-10 and plasma granulocyte-colony-stimulating factor, myeloperoxidase, and calprotectin also increased during exercise in all trials but did not differ significantly between the carbohydrate and placebo trials. Plasma norepinephrine concentration increased during exercise in all trials and was significantly higher (50%, p = .01) after the carbohydrate vs. the placebo trial in 32 degrees C. CONCLUSION: Carbohydrate ingestion attenuated neutrophil counts during exercise in hot conditions, whereas it had no effect on any other immune variables in either temperate or hot conditions.

Avoiding uninformed responses in destination image questionnaires

Since the first destination image studies were published in the early 1970s, the field has become one of the most popular in the tourism literature. While reviews of the destination image literature show no commonly agreed conceptualisation of the construct, researchers have predominantly used structured questionnaires for measurement. There has been criticism that the way some of these scales have been selected means a greater likelihood of attributes being irrelevant to participants. This opens up the risk of stimulating uninformed responses. The issue of uninformed response was first raised as a source of error 60 years ago. However, there has been little, if any, discussion in relation to destination image measurement, studies of which often require participants to provide opinion-driven rather than fact-based responses. This paper reports the trial of a ‘don’t know’ (DK) non-response option for participants in two destination image questionnaires. It is suggested the use of a DK option provides participants with an alternative to i) skipping the question, ii) using the scale midpoint to denote neutrality, or iii) providing an uninformed response. High levels of DK usage by participants can then alert the marketer of the need to improve awareness of destination performance for potential salient attributes.

The enactment of formative assessment in English language classrooms in two Chinese universities : teacher and student responses

The College English Curriculum Requirements (CECR), announced by the Chinese Ministry of Education in 2007, recommended the inclusion of formative assessment into the existing summative assessment framework of College English. This policy had the potential to fundamentally change the nature of assessment and its role in the teaching and learning of English in Chinese universities. In order to document and analyse these changes, case studies involving English language teachers and learners were undertaken in two Chinese Universities: one a Key university in the national capital; the other a non-Key university in a western province. The case study design incorporated classroom observations and interviews with English language teachers and their students. The type and focus of feedback and the engagement of students in assessment were analysed in the two contexts. Fundamental to the analysis was the concept of enactment, with the focus of this study on the ways that policy ideas and principles were enacted in the practices of the Chinese university classroom. Understandings of formative assessment as applied in contexts other than the predominantly Western, Anglophone contexts from where many of its principles derive, are offered.

Adaption of horses to a novel dynamic feeding system : movement and behavioural responses

Reasons for performing study: Many domestic horses and ponies are sedentary and obese due to confinement to small paddocks and stables and a diet of infrequent, high-energy rations. Severe health consequences can be associated with this altered lifestyle. Objectives: The aims of this study were to investigate the ability of horses to learn to use a dynamic feeder system and determine the movement and behavioural responses of horses to the novel system. Methods: A dynamic feed station was developed to encourage horses to exercise in order to access ad libitum hay. Five pairs of horses (n = 10) were studied using a randomised crossover design with each pair studied in a control paddock containing a standard hay feeder and an experimental paddock containing the novel hay feeder. Horse movement was monitored by a global positioning system (GPS) and horses observed and their ability to learn to use the system and the behavioural responses to its use assessed. Results: With initial human intervention all horses used the novel feeder within 1 h. Some aggressive behaviour was observed between horses not well matched in dominance behaviour. The median distance walked by the horses was less (P = 0.002) during a 4 h period (117 [57–185] m) in the control paddock than in the experimental paddock (630 [509–719] m). Conclusions: The use of an automated feeding system promotes increased activity levels in horses housed in small paddocks, compared with a stationary feeder.

Endocrine and immune responses to resistance training in prostate cancer patients

This study examined the effect of 20 weeks resistance training on a range of serum hormones and inflammatory markers at rest, and following acute bouts of exercise in prostate cancer patients undergoing androgen deprivation. Ten patients exercised twice weekly at high intensity for several upper and lower-body muscle groups. Neither testosterone nor prostate-specific antigen changed at rest or following an acute bout of exercise. However, serum growth hormone (GH), dehydroepiandrosterone (DHEA), interleukin-6, tumor necrosis factor-alpha and differential blood leukocyte counts increased (P < 0.05) following acute exercise. Resistance exercise does not appear to compromise testosterone suppression, and acute elevations in serum GH and DHEA may partly underlie improvements observed in physical function.

Characterization of inflammatory responses to eccentric exercise in humans

Eccentric exercise commonly results in muscle damage. The primary sequence of events leading to exercise-induced muscle damage is believed to involve initial mechanical disruption of sarcomeres, followed by impaired excitation-contraction coupling and calcium signaling, and finally, activation of calcium-sensitive degradation pathways. Muscle damage is characterized by ultrastructural changes to muscle architecture, increased muscle proteins and enzymes in the bloodstream, loss of muscular strength and range of motion and muscle soreness. The inflammatory response to exercise-induced muscle damage is characterized by leukocyte infiltration and production of pro-inflammatory cytokines within damaged muscle tissue, systemic release of leukocytes and cytokines, in addition to alterations in leukocyte receptor expression and functional activity. Current evidence suggests that inflammatory responses to muscle damage are dependent on the type of eccentric exercise, previous eccentric loading (repeated bouts), age and gender. Circulating neutrophil counts and systemic cytokine responses are greater after eccentric exercise using a large muscle mass (e.g. downhill running, eccentric cycling) than after other types of eccentric exercise involving a smaller muscle mass. After an initial bout of eccentric exercise, circulating leukocyte counts and cell surface receptor expression are attenuated. Leukocyte and cytokine responses to eccentric exercise are impaired in elderly individuals, while cellular infiltration into skeletal muscle is greater in human females than males after eccentric exercise. Whether alterations in intracellular calcium homeostasis influence inflammatory responses to muscle damage is uncertain. Furthermore, the effects of antioxidant supplements are variable, and the limited data available indicates that anti-inflammatory drugs largely have no influence on inflammatory responses to eccentric exercise. In this review, we compare local versus systemic inflammatory responses, and discuss some of the possible mechanisms regulating the inflammatory responses to exercise-induced muscle damage in humans.

Exercise-induced alterations in neutrophil degranulation and respiratory burst activity : possible mechanisms of action

Neutrophils constitute 50-60% of all circulating leukocytes; they present the first line of microbicidal defense and are involved in inflammatory responses. To examine immunocompetence in athletes, numerous studies have investigated the effects of exercise on the number of circulating neutrophils and their response to stimulation by chemotactic stimuli and activating factors. Exercise causes a biphasic increase in the number of neutrophils in the blood, arising from increases in catecholamine and cortisol concentrations. Moderate intensity exercise may enhance neutrophil respiratory burst activity, possibly through increases in the concentrations of growth hormone and the inflammatory cytokine IL-6. In contrast, intense or long duration exercise may suppress neutrophil degranulation and the production of reactive oxidants via elevated circulating concentrations of epinephrine (adrenaline) and cortisol. There is evidence of neutrophil degranulation and activation of the respiratory burst following exercise-induced muscle damage. In principle, improved responsiveness of neutrophils to stimulation following exercise of moderate intensity could mean that individuals participating in moderate exercise may have improved resistance to infection. Conversely, competitive athletes undertaking regular intense exercise may be at greater risk of contracting illness. However, there are limited data to support this concept. To elucidate the cellular mechanisms involved in the neutrophil responses to exercise, researchers have examined changes in the expression of cell membrane receptors, the production and release of reactive oxidants and more recently, calcium signaling. The investigation of possible modifications of other signal transduction events following exercise has not been possible because of current methodological limitations. At present, variation in exercise-induced alterations in neutrophil function appears to be due to differences in exercise protocols, training status, sampling points and laboratory assay techniques.