Cytokine synthesis by intestinal intraepithelial lymphocytes. Both gamma/delta T cell receptor-positive and alpha/beta T cell receptor-positive T cells in the G1 phase of cell cycle produce IFN-gamma and IL-5

Murine intestinal intraepithelial lymphocytes (IEL) have been shown to contain subsets of alpha/beta TCR+ and gamma/delta TCR+ T cells that spontaneously produce cytokines such as IFN-gamma and IL-5. We have now determined the nature and cell cycle stage of these cytokine-producing T lymphocytes in EIL by using IFN-gamma- and IL-5-specific ELISPOT assay, cytokine-specific mRNA-cDNA dot-blot hybridization and polymerase chain reaction, and flow cytometry (FACS) for DNA analysis. When CD3+ T cells from IEL of normal C3H/HeN mice were separated into low and high density fractions by discontinuous Percoll gradients, IFN-gamma and IL-5 spot-forming cells were only found in the former population. Analysis of mRNA for these cytokines by both IFN-gamma- and IL-5-specific dot-blot hybridization and polymerase chain reaction revealed that higher levels of message for IFN-gamma and IL-5 were also seen in the low density fraction. However, cell cycle analysis of these two fractions by FACS using propidium iodide showed a similar pattern of cell cycle stages in both low and high density populations (G0 + G1 approximately 96 to 98% and S/G2 + M approximately 2 to 4%). Finally, mRNA from gamma/delta TCR+ and alpha/beta TCR+ T cells in both low and high density fractions of IEL were analyzed for IFN-gamma and IL-5 message by polymerase chain reaction. After 35 cycles of amplification, both gamma/delta TCR+ and alpha/beta TCR+ T cells in the low density fraction expressed higher levels of message for these two cytokines when compared with the high density population. These results have now shown that both gamma/delta and alpha/beta TCR+ IEL can be separated into low and high density subsets and both fractions possess a similar stage of cell cycle. However, only the low density cells (in G1 phase) of both gamma/delta and alpha/beta TCR types possess increased cytokine-specific mRNA and produce the cytokines IFN-gamma and IL-5. Our results suggest that alpha/beta TCR+ and gamma/delta TCR+ IEL can produce cytokines without cell proliferation.

The Ghrelin axis : does it have an appetite for cancer progression?

Ghrelin, the endogenous ligand for the GH secretagogue receptor (GHSR), is a peptide hormone with diverse physiological roles. Ghrelin regulates GH release, appetite and feeding, gut motility, and energy balance and also has roles in the cardiovascular, immune, and reproductive systems. Ghrelin and the GHSR are expressed in a wide range of normal and tumor tissues, and a fluorescein-labeled, truncated form of ghrelin is showing promise as a biomarker for prostate cancer. Plasma ghrelin levels are generally inversely related to body mass index and are unlikely to be useful as a biomarker for cancer, but may be useful as a marker for cancer cachexia. Some single nucleotide polymorphisms in the ghrelin and GHSR genes have shown associations with cancer risk; however, larger studies are required. Ghrelin regulates processes associated with cancer, including cell proliferation, apoptosis, cell migration, cell invasion, inflammation, and angiogenesis; however, the role of ghrelin in cancer is currently unclear. Ghrelin has predominantly antiinflammatory effects and may play a role in protecting against cancer-related inflammation. Ghrelin and its analogs show promise as treatments for cancer-related cachexia. Further studies using in vivo models are required to determine whether ghrelin has a role in cancer progression.

Cloning of a novel insulin-regulated ghrelin transcript in prostate cancer

Ghrelin is a multifunctional hormone, with roles in stimulating appetite and regulating energy balance, insulin secretion and glucose homeostasis. The ghrelin gene locus (GHRL) is highly complex and gives rise to a range of novel transcripts derived from alternative first exons and internally spliced exons. The wild-type transcript encodes a 117 amino acid preprohormone that is processed to yield the 28 amino acid peptide ghrelin. Here, we identified insulin-responsive transcription corresponding to cryptic exons in intron 2 of the human ghrelin gene. A transcript, termed in2c-ghrelin (intron 2-cryptic), was cloned from the testis and the LNCaP prostate cancer cell line. This transcript may encode an 83 AA preproghrelin isoform that codes for the ghrelin, but not obestatin. It is expressed in a limited number of normal tissues and in tumours of the prostate, testis, breast and ovary. Finally, we confirmed that in2c-ghrelin transcript expression, as well as the recently described in1-ghrelin transcript, is significantly upregulated by insulin in cultured prostate cancer cells. Metabolic syndrome and hyperinsulinaemia has been associated with prostate cancer risk and progression. This may be particularly significant after androgen deprivation therapy for prostate cancer, which induces hyperinsulinaemia, and this could contribute to castrate resistant prostate cancer growth. We have previously demonstrated that ghrelin stimulates prostate cancer cell line proliferation in vitro. This study is the first description of insulin regulation of a ghrelin transcript in cancer, and should provide further impetus for studies into the expression, regulation and function of ghrelin gene products.

Fatalism, superstition, religion, and culture : road user beliefs and behaviour in Pakistan

Road traffic crashes have emerged as a major health problem around the world. Road crash fatalities and injuries have been reduced significantly in developed countries, but they are still an issue in low and middle-income countries. The World Health Organization (WHO, 2009) estimates that the death toll from road crashes in low- and middle-income nations is more than 1 million people per year, or about 90% of the global road toll, even though these countries only account for 48% of the world's vehicles. Furthermore, it is estimated that approximately 265,000 people die every year in road crashes in South Asian countries and Pakistan stands out with 41,494 approximately deaths per year. Pakistan has the highest rate of fatalities per 100,000 population in the region and its road crash fatality rate of 25.3 per 100,000 population is more than three times that of Australia's. High numbers of road crashes not only cause pain and suffering to the population at large, but are also a serious drain on the country's economy, which Pakistan can ill-afford. Most studies identify human factors as the main set of contributing factors to road crashes, well ahead of road environment and vehicle factors. In developing countries especially, attention and resources are required in order to improve things such as vehicle roadworthiness and poor road infrastructure. However, attention to human factors is also critical. Human factors which contribute to crashes include high risk behaviours like speeding and drink driving, and neglect of protective behaviours such as helmet wearing and seat belt wearing. Much research has been devoted to the attitudes, beliefs and perceptions which contribute to these behaviours and omissions, in order to develop interventions aimed at increasing safer road use behaviours and thereby reducing crashes. However, less progress has been made in addressing human factors contributing to crashes in developing countries as compared to the many improvements in road environments and vehicle standards, and this is especially true of fatalistic beliefs and behaviours. This is a significant omission, since in different cultures in developing countries there are strong worldviews in which predestination persists as a central idea, i.e. that one's life (and death) and other events have been mapped out and are predetermined. Fatalism refers to a particular way in which people regard the events that occur in their lives, usually expressed as a belief that an individual does not have personal control over circumstances and that their lives are determined through a divine or powerful external agency (Hazen & Ehiri, 2006). These views are at odds with the dominant themes of modern health promotion movements, and present significant challenges for health advocates who aim to avert road crashes and diminish their consequences. The limited literature on fatalism reveals that it is not a simple concept, with religion, culture, superstition, experience, education and degree of perceived control of one's life all being implicated in accounts of fatalism. One distinction in the literature that seems promising is the distinction between empirical and theological fatalism, although there are areas of uncertainty about how well-defined the distinction between these types of fatalism is. Research into road safety in Pakistan is scarce, as is the case for other South Asian countries. From the review of the literature conducted, it is clear that the descriptions given of the different belief systems in developing countries including Pakistan are not entirely helpful for health promotion purposes and that further research is warranted on the influence of fatalism, superstition and other related beliefs in road safety. Based on the information available, a conceptual framework is developed as a means of structuring and focusing the research and analysis. The framework is focused on the influence of fatalism, superstition, religion and culture on beliefs about crashes and road user behaviour. Accordingly, this research aims to provide an understanding of the operation of fatalism and related beliefs in Pakistan to assist in the development and implementation of effective and culturally appropriate interventions. The research examines the influence of fatalism, superstition, religious and cultural beliefs on risky road use in Pakistan and is guided by three research questions: 1. What are the perceptions of road crash causation in Pakistan, in particular the role of fatalism, superstition, religious and cultural beliefs? 2. How does fatalism, superstition, and religious and cultural beliefs influence road user behaviour in Pakistan? 3. Do fatalism, superstition, and religious and cultural beliefs work as obstacles to road safety interventions in Pakistan? To address these questions, a qualitative research methodology was developed. The research focused on gathering data through individual in-depth interviewing using a semi-structured interview format. A sample of 30 participants was interviewed in Pakistan in the cities of Lahore, Rawalpindi and Islamabad. The participants included policy makers (with responsibility for traffic law), experienced police officers, religious orators, professional drivers (truck, bus and taxi) and general drivers selected through a combination of purposive, criterion and snowball sampling. The transcripts were translated from Urdu and analysed using a thematic analysis approach guided by the conceptual framework. The findings were divided into four areas: attribution of crash causation to fatalism; attribution of road crashes to beliefs about superstition and malicious acts; beliefs about road crash causation linked to popular concepts of religion; and implications for behaviour, safety and enforcement. Fatalism was almost universally evident, and expressed in a number of ways. Fate was used to rationalise fatal crashes using the argument that the people killed were destined to die that day, one way or another. Related to this was the sense of either not being fully in control of the vehicle, or not needing to take safety precautions, because crashes were predestined anyway. A variety of superstitious-based crash attributions and coping methods to deal with road crashes were also found, such as belief in the role of the evil eye in contributing to road crashes and the use of black magic by rivals or enemies as a crash cause. There were also beliefs related to popular conceptions of religion, such as the role of crashes as a test of life or a source of martyrdom. However, superstitions did not appear to be an alternative to religious beliefs. Fate appeared as the 'default attribution' for a crash when all other explanations failed to account for the incident. This pervasive belief was utilised to justify risky road use behaviour and to resist messages about preventive measures. There was a strong religious underpinning to the statement of fatalistic beliefs (this reflects popular conceptions of Islam rather than scholarly interpretations), but also an overlap with superstitious and other culturally and religious-based beliefs which have longer-standing roots in Pakistani culture. A particular issue which is explored in more detail is the way in which these beliefs and their interpretation within Pakistani society contributed to poor police reporting of crashes. The pervasive nature of fatalistic beliefs in Pakistan affects road user behaviour by supporting continued risk taking behaviour on the road, and by interfering with public health messages about behaviours which would reduce the risk of traffic crashes. The widespread influence of these beliefs on the ways that people respond to traffic crashes and the death of family members contribute to low crash reporting rates and to a system which appears difficult to change. Fate also appeared to be a major contributing factor to non-reporting of road crashes. There also appeared to be a relationship between police enforcement and (lack of) awareness of road rules. It also appears likely that beliefs can influence police work, especially in the case of road crash investigation and the development of strategies. It is anticipated that the findings could be used as a blueprint for the design of interventions aimed at influencing broad-spectrum health attitudes and practices among the communities where fatalism is prevalent. The findings have also identified aspects of beliefs that have complex social implications when designing and piloting driver intervention strategies. By understanding attitudes and behaviours related to fatalism, superstition and other related concepts, it should be possible to improve the education of general road users, such that they are less likely to attribute road crashes to chance, fate, or superstition. This study also underscores the understanding of this issue in high echelons of society (e.g., policy makers, senior police officers) as their role is vital in dispelling road users' misconceptions about the risks of road crashes. The promotion of an evidence or scientifically-based approach to road user behaviour and road safety is recommended, along with improved professional education for police and policy makers.

The roles of procedural justice and social learning in improving self organizing capabilities of local communities for sustainable development in decentralized Indonesia

The development planning process under Law No. 25/2004 is said to be a new approach to increase public participation in decentralised Indonesia. This Law has introduced planning mechanisms, called Musyawarah Perencanaan Pembangunan (Musrenbang), to provide a forum for development planning. In spite of the expressed intention of these mechanisms to improve public participation, some empirical observations have cast doubt on the outcomes. As a result, some local governments have tried to provide alternative mechanisms to promote for participation in local development planning. Since planning is often said to be one of the most effective ways to improve community empowerment, it is of particular concern, to examine the extent to which the current local development planning processes in Indonesia provide sufficient opportunities to improve the self organising capabilities of communities to sustain development programs to meet local needs. With this objective in mind, this paper examines problems encountered by the new local planning mechanism (Musrenbang) in increasing local community empowerment particularly regarding their self organising capabilities. The concept of community empowerment as a pathway to social justice is explored to identify its key elements and approaches and to show how they can be incorporated within planning processes. Having discussed this, it is then argued that to change current unfavorable outcomes, procedural justice and social learning approaches need to be adopted as pathways to community empowerment. Lastly it is also suggested that an alternative local planning process, called Sistem Dukungan (SISDUK), introduced in South Suluwezi in collaboration with JAICA in 2006 (?) offers scope to incorporate such procedural justice and social learning approaches to improve the self organizing capabilities of local communities.

Emotional arousal of beginning physics teachers during extended experimental investigations

Teachers often have difficulty implementing inquiry-based activities, leading to the arousal of negative emotions. In this multicase study of beginning physics teachers in Australia, we were interested in the extent to which their expectations were realized and how their classroom experiences while implementing extended experimental investigations (EEIs) produced emotional states that mediated their teaching practices. Against rhetoric of fear expressed by their senior colleagues, three of the four teachers were surprised by the positive outcomes from their supervision of EEIs for the first time. Two of these teachers experienced high intensity positive emotions in response to their students’ success. When student actions / outcomes did not meet their teachers’ expectations, frustration, anger, and disappointment were experienced by the teachers, as predicted by a sociological theory of human emotions (Turner, 2007). Over the course of the EEI projects, the teachers’ practices changed along with their emotional states and their students’ achievements. We account for similarities and differences in the teachers’ emotional experiences in terms of context, prior experience, and expectations. The findings from this study provide insights into effective supervision practices that can be used to inform new and experienced teachers alike.

Untanglings: A novel approach to analyzing concurrent systems

Substantial research efforts have been expended to deal with the complexity of concurrent systems that is inherent to their analysis, e.g., works that tackle the well-known state space explosion problem. Approaches differ in the classes of properties that they are able to suitably check and this is largely a result of the way they balance the trade-off between analysis time and space employed to describe a concurrent system. One interesting class of properties is concerned with behavioral characteristics. These properties are conveniently expressed in terms of computations, or runs, in concurrent systems. This article introduces the theory of untanglings that exploits a particular representation of a collection of runs in a concurrent system. It is shown that a representative untangling of a bounded concurrent system can be constructed that captures all and only the behavior of the system. Representative untanglings strike a unique balance between time and space, yet provide a single model for the convenient extraction of various behavioral properties. Performance measurements in terms of construction time and size of representative untanglings with respect to the original specifications of concurrent systems, conducted on a collection of models from practice, confirm the scalability of the approach. Finally, this article demonstrates practical benefits of using representative untanglings when checking various behavioral properties of concurrent systems.

Making sense of mental illness as a full human experience : Perspective of illness and recovery held by people with a mental illness living in the community.

Recovery is a highly contextualized concept amid divergent interpretations and unique experiences. There is substantial current interest in building evidence about recovery from mental illness in order to inform best practice founded in the ways people find to live productive and meaningful lives. This paper presents some accounts related to recovery and illness expressed by eight people through a Participatory Action Research project. The research facilitated entry to the subjective experiences of living in the community as an artist with a mental illness. The people in the research shared an integrated understanding of illness, recovery and identity. Their understanding provided insight into mental illness as an inseparable aspect of who they were. Further, specific issue was raised of recovery as a clinical term with a requirement to meet distinct conventions of recovery. This paper emphasizes that being ill and being well, for the person with a mental illness, is a dynamic and complex development not easily explained or transformed into uniform process or outcomes. Attempts to establish an integral or consensual approach to recovery has, to date, disregarded mental illness as a full human experience. This paper argues that broader frameworks for thinking and responding to the dynamic processes of mental illness and recovery are needed and require acknowledgment of competing and contradictory ideas.

Bouncing back : homegrown. Curated exhibition of student work and design workshop

Bouncing Back Architecture Exhibition: This exhibition showcases interpretations of urban resiliency by 2nd and 4th Year undergraduate architecture students who explore the notion of Bouncing Back from the 2011 Queensland floods, in the context of contemporary Brisbane built environment. Design solutions have been expressed in a variety of forms including emergency shelters, flood-proof housing and a range of urban designs, some of which address extreme environmental conditions. Design Process Workshop | Architecture Workshop with Queensland Academy of Creative Industries Students: In collaboration with Homegrown Facilitator Natalie Wright, Lindy Osborne and Glenda Caldwell and some of their architecture students from the QUT School of Design, extended the university design studio experience to 18 Secondary School students, who brainstormed and designed emergency food distribution shelters for those affected by floods. Designs and models created in the workshop were subsequently included in the Bouncing Back Architecture Exhibition.

Human rights, the law, cyber-security and democracy : after the European Convention

Many commentators have treated the internet as a site of democratic freedom and as a new kind of public sphere. While there are good reasons for optimism, like any social space digital space also has its dark side. Citizens and governments alike have expressed anxiety about cybercrime and cyber-security. In August 2011, the Australian government introduced legislation to give effect to Australia becoming a signatory to the European Convention on Cybercrime (2001). At the time of writing, that legislation is still before the Parliament. In this article, attention is given to how the legal and policy-making process enabling Australia to be compliant with the European Convention on Cybercrime came about. Among the motivations that informed both the development of the Convention in Europe and then the Australian exercise of legislating for compliance with it was a range of legitimate concerns about the impact that cybercrime can have on individuals and communities. This article makes the case that equal attention also needs to be given to ensuring that legislators and policy makers differentiate between legitimate security imperatives and any over-reach evident in the implementation of this legislation that affects rule of law principles, our capacity to engage in democratic practices, and our civic and human rights.

Paclitaxel resistance and multicellular spheroid formation are induced by kallikrein-related peptidase 4 in serous ovarian cancer cells in an ascites mimicking microenvironment

High tumor kallikrein-related-peptidase 4 (KLK4) levels are associated with a poor outcome for women with serous epithelial ovarian cancer (EOC), for which peritoneal dissemination and chemoresistance are key events. To determine the role of KLK4 in these events, we examined KLK4-transfected SKOV-3 and endogenous KLK4 expressing OVCA432 cells in 3-dimensional (3D) suspension culture to mimic the ascites microenvironment. KLK4-SKOV-3 cells formed multicellular aggregates (MCAs) as seen in ascites, as did SKOV-3 cells treated with active KLK4. MCA formation was reduced by treatment with a KLK4 blocking antibody or the selective active site KLK4 sunflower trypsin inhibitor (SFTI-FCQR). KLK4-MCAs formed larger cancer cell foci in mesothelial cell monolayers than those formed by vector and native SKOV-3 cells, suggesting KLK4-MCAs are highly invasive in the peritoneal microenvironment. A high level of KLK4 is expressed by ascitic EOC cells compared to matched primary tumor cells, further supporting its role in the ascitic microenvironment. Interestingly, KLK4 transfected SKOV-3 cells expressed high levels of the KLK4 substrate, urokinase plasminogen activator (uPA), particularly in 3D-suspension, and high levels of both KLK4 and uPA were observed in patient cells taken from ascites. Importantly, the KLK4-MCAs were paclitaxel resistant which was reversed by SFTI-FCQR and to a lesser degree by the general serine protease inhibitor, Aprotinin, suggesting that in addition to uPA, other as yet unidentified substrates of KLK4 must be involved. Nonetheless, these data suggest that KLK4 inhibition, in conjunction with paclitaxel, may improve the outcome for women with serous epithelial ovarian cancer and high KLK4 levels in their tumors.

Characteristics of culturally and linguistically diverse mental health clients

The present study examined Queensland Transcultural Mental Health Centre (QTMHC) client characteristics in order to provide a better understanding for development of future health service delivery models. Archived data that was collected for 1499 clients over two years period (2007-2009) was analysed using descriptive statistics and Chi squares. The results indicated that clients were referred from a range of sources and were generally adults. There were more women than men, who sought services. At least half of the clients had language barriers and relied on bilingual workers. Most frequently expressed mental health issues were mood disorder symptoms, followed by symptoms of schizophrenia and psychosis and anxiety. Acculturation strains and stressors were described as the most common psychosocial issues. Mental health and psychosocial issues differed for age, gender and world regions from which the CALD clients originated. The findings provided an understanding of clients who seek services at QTMHC. Various ways in which transcultural services and data bases can be further improved are discussed.

Temporal summation of intrinsically photosensitive retinal ganglion cell (ipRGC) contributions to the human pupil.

Purpose: IpRGCs mediate non-image forming functions including photoentrainment and the pupil light reflex (PLR). Temporal summation increases visual sensitivity and decreases temporal resolution for image forming vision, but the summation properties of nonimage forming vision are unknown. We investigated the temporal summation of inner (ipRGC) and outer (rod/cone) retinal inputs to the PLR. Method: The consensual PLR of the left eye was measured in six participants with normal vision using a Maxwellian view infrared pupillometer. Temporal summation was investigated using a double-pulse protocol (100 ms stimulus pairs; 0–1024 ms inter-stimulus interval, ISI) presented to the dilated fellow right eye (Tropicamide 1%). Stimulus lights (blue λmax = 460 nm; red λmax = 638 nm) biased activity to inneror outer retinal inputs to non-image forming vision. Temporal summation was measured suprathreshold (15.2 log photons.cm−2.s−1 at the cornea) and subthreshold (11.4 log photons.cm−2.s−1 at the cornea). Results: RM-ANOVAs showed the suprathreshold and subthreshold 6 second post illumination pupil response (PIPR: expressed as percentage baseline diameter) did not significantly vary for red or blue stimuli (p > .05). The PIPR for a subthreshold red 16 ms double-pulse control condition did not significantly differ with ISI (p > .05). The maximum constriction amplitude for red and blue 100 ms double- pulse stimuli did not significantly vary with ISI (p > .05). Conclusion: The non-significant changes in suprathreshold PIPR and subthreshold maximum pupil constriction indicate that inner retinal ipRGC inputs and outer retinal photoreceptor inputs to the PLR do not show temporal summation. The results suggest a fundamental difference between the temporal summation characteristics of image forming and non-image forming vision.

Effects of rice husk biochar and sugar-mill by-products on methane consumption from two different soils

Methane (CH4) is an important greenhouse gas with a global warming potential (GWP) 25 times greater than carbon dioxide (CO2) that can be produced or consumed in soils depending on environmental conditions and other factors. Biochar application to soils has been shown to reduce CH4 emissions and to increase CH4 consumption. However, the effects of rice husk biochar (RB) have not been thoroughly investigated. Two 60-day laboratory incubation experiments were conducted to investigate the effects of amending two soil types with RB, raw mill mud (MM) and composted mill mud (CM) on soil CH4 consumption and emissions. Soil cores incubated in 1 L glass jars and gas samples were analysed for CH4 using gas chromatography. Average CH4 consumption rates varied from -0.06 to -0.68 g CH4-C( )/ha/d in sandy loam soil and -0.59 to -1.00 g CH4-C/ha/d in clay soil. Application of RB resulted in CH4 uptake of -0.52 to -0.55 g CH4-C/ha/d in sandy loam and -0.76 to -0.91 g CH4-C/ha/d in clay soil. Addition of MM showed low CH4 emissions or consumption at 60% water-filled pore space (WFPS) in both soils. However, at high water contents (>75% WFPS) the application of MM produced high rates of CH4 emissions which were significantly suppressed when RB was added. Cumulative emissions of the MM treatment produced 108.9 g CH4-C/ha at 75% WFPS and 11 459.3 g CH4-C/ha at 90% WFPS in sandy loam soil over a period of 60 days. RB can increase CH4 uptake under low soil water content (SWC) and decrease CH4 emissions under anaerobic conditions. CM expressed more potential to reduce CH4 emissions than those of MM.

Modelling the flow of juice through a mill

A juice flow model has been developed to estimate the juice expression at the four nips of a sixroller mill. An extended volumetric theory was applied to determine the juice expressed at each nip. The model was applied to a first and final mill, using typical mill settings and an empirical equation to estimate reabsorption. Results of using the model for typical heavy-duty pressure feeder settings show that most of the juice is expressed at the pressure feeder nip. Since the pressure feeders are remote from the mill, a significant portion of the juice is expressed before the bagasse enters the mill.