Evolution of JAK-STAT pathway components : mechanisms and role in immune system development

Background
Lying downstream of a myriad of cytokine receptors, the Janus kinase (JAK) – Signal transducer and activator of transcription (STAT) pathway is pivotal for the development and function of the immune system, with additional important roles in other biological systems. To gain further insight into immune system evolution, we have performed a comprehensive bioinformatic analysis of the JAK-STAT pathway components, including the key negative regulators of this pathway, the SH2-domain containing tyrosine phosphatase (SHP), Protein inhibitors against Stats (PIAS), and Suppressor of cytokine signaling (SOCS) proteins across a diverse range of organisms.

Results
Our analysis has demonstrated significant expansion of JAK-STAT pathway components co-incident with the emergence of adaptive immunity, with whole genome duplication being the principal mechanism for generating this additional diversity. In contrast, expansion of upstream cytokine receptors appears to be a pivotal driver for the differential diversification of specific pathway components.

Conclusion
Diversification of JAK-STAT pathway components during early vertebrate development occurred concurrently with a major expansion of upstream cytokine receptors and two rounds of whole genome duplications. This produced an intricate cell-cell communication system that has made a significant contribution to the evolution of the immune system, particularly the emergence of adaptive immunity.

Impact of nest sanitation on the immune system of parents and nestlings in a passerine bird

Bacterial communities are thought to have fundamental effects on the growth and development of nestling birds. The antigen exposure hypothesis suggests that, for both nestlings and adult birds, exposure to a diverse range of bacteria would select for stronger immune defences. However, there are relatively few studies that have tested the immune/bacterial relationships outside of domestic poultry. We therefore sought to examine indices of immunity (microbial killing ability in naïve birds, which is a measure of innate immunity and the antibody response to sheep red blood cells, which measures adaptive immunity) in both adult and nestling zebra finches (Taeniopygia guttata). We did this throughout breeding and between reproductive attempts in nests that were experimentally manipulated to change the intensity of bacterial exposure. Our results suggest that nest sanitation and bacterial load affected measures of the adaptive immune system, but not the innate immune parameters tested. Adult finches breeding in clean nests had a lower primary antibody response to sheep red blood cells (SRBC), particularly males, and a greater difference between primary and secondary responses. Adult microbial killing of E.coli decreased as parents moved from incubation to nestling rearing for both nest treatments; however, killing of C.albicans remained consistent throughout. In nestlings, both innate microbial killing and the adaptive antibody response did not differ between nest environments. Together, these results suggest that the exposure to microorganisms in the environment affect the adaptive immune system in nesting birds, with exposure upregulating the antibody response in adult birds.

Sindbis virus vectors elicit hemagglutinin-specific humoral and cellular immune responses and offer a dose-sparing strategy for vaccination

We report here on the use of a Sindbis virus-based DNA-launch RNA replicon vector (pSIN-HA) that expresses influenza hemagglutinin (HA) as an immunogen. Immunization of mice with pSIN-HA generated anti-HA antibody and CTL responses and resulted in lower lung viral titers after influenza challenge when compared to controls. Importantly, immunization with a low dose of pSIN-HA mediated significantly reduced lung viral titers following challenge at 43 weeks after the final immunization. In contrast, immunization with a non-replicon DNA vector expressing HA failed to mediate reduced lung viral titer at the same dose. This demonstrated the dose-sparing capacity of the SIN vector system and its ability to stimulate long-term memory responses, properties that are highly desirable in any vaccine formulation.

Functional similarities between pigeon 'milk' and mammalian milk : induction of immune gene expression and modification of the microbiota

Pigeon ‘milk’ and mammalian milk have functional similarities in terms of nutritional benefit and delivery of immunoglobulins to the young. Mammalian milk has been clearly shown to aid in the development of the immune system and microbiota of the young, but similar effects have not yet been attributed to pigeon ‘milk’. Therefore, using a chicken model, we investigated the effect of pigeon ‘milk’ on immune gene expression in the Gut Associated Lymphoid Tissue (GALT) and on the composition of the caecal microbiota. Chickens fed pigeon ‘milk’ had a faster rate of growth and a better feed conversion ratio than control chickens. There was significantly enhanced expression of immune-related gene pathways and interferon-stimulated genes in the GALT of pigeon ‘milk’-fed chickens. These pathways include the innate immune response, regulation of cytokine production and regulation of B cell activation and proliferation. The caecal microbiota of pigeon ‘milk’-fed chickens was significantly more diverse than control chickens, and appears to be affected by prebiotics in pigeon ‘milk’, as well as being directly seeded by bacteria present in pigeon ‘milk’. Our results demonstrate that pigeon ‘milk’ has further modes of action which make it functionally similar to mammalian milk. We hypothesise that pigeon ‘lactation’ and mammalian lactation evolved independently but resulted in similarly functional products.

Malicious code detection architecture inspired by human immune system

Malicious code is a threat to computer systems globally. In this paper, we outline the evolution of malicious code attacks. The threat is evolving, leaving challenges for attackers to improve attack techniques and for researchers and security specialists to improve detection accuracy. We present a novel architecture for an effective defense against malicious code attack, inspired by the human immune system. We introduce two phases of program execution: Adolescent and Mature Phase. The first phase uses a malware profile matching mechanism, whereas the second phase uses a program profile matching mechanism. Both mechanisms are analogous to the innate immune system

Immune-microbiota interactions: dysbiosis as a global health issue

Throughout evolution, microbial genes and metabolites have become integral to virtually all aspects of host physiology, metabolism and even behaviour. New technologies are revealing sophisticated ways in which microbial communities interface with the immune system, and how modern environmental changes may be contributing to the rapid rise of inflammatory noncommunicable diseases (NCDs) through declining biodiversity. The implications of the microbiome extend to virtually every branch of medicine, biopsychosocial and environmental sciences. Similarly, the impact of changes at the immune-microbiota interface are directly relevant to broader discussions concerning rapid urbanization, antibiotics, agricultural practices, environmental pollutants, highly processed foods/beverages and socioeconomic disparities--all implicated in the NCD pandemic. Here, we make the argument that dysbiosis (life in distress) is ongoing at a micro- and macro-scale and that as a central conduit of health and disease, the immune system and its interface with microbiota is a critical target in overcoming the health challenges of the twenty-first century.

Valuation and reporting of native fauna in monetary terms: compatibility between a market-Based system and natural resources?

A change in community values and priorities has introduced ethical,
environmental and social issues into the way in which business conducts
its activities. There are an increasing number of managed investment funds focusing on socially responsible investment (SRI) by concentrating on firms that operate according to predetermined criteria for environmental, social and ethical issues. For investors in these funds environmental stewardship issues are integrated with concern over financial resources and performance. In this paper the accounting and reporting by business activities concerned with conservation of wildlife are examined. The world of accounting has functioned for many years with relatively few accounting standards devoted to specialised industry needs. In 1998 the Australian Accounting Standards Board and in 2001 the International Accounting Standards Board issued standards devoted to agriculture. Both standards deal with the reporting of managed biological assets and require application of essentially the same approaches despite the Australian standard requiring net market value while the International standard requires fair value. In this paper we analyse how one conservation firm Earth Sanctuaries Ltd. (ESL) has applied AASB 1037 and then we explore the implications for conservation firms operating in geographical locations outside Australia. It is suggested that AASB 1037 and indeed lAS 41 may not provide value appropriate information for investor decisions relating to accounting profits for such firms. Our examination shows that it is appropriate to reconsider accounting guidelines provided by these standards in order to link the information relating to economic and environmental performance. Transparency may be improved by a move closer to Elkington 's (1997) triple bottom line reporting. We therefore contend that the issues arising from the use ofAASB 1037 and lAS 41 need to be widely considered by all standard setters, particularly given the increasing attention to SRI.

Vascular attack by 5,6-dimethylxanthenone-4-acetic acid combined with B7.1 (CD80)-mediated immunotherapy overcomes immune resistance and leads to the eradication of large tumors and multiple tumor foci

The promise of cancer immunotherapy is that it will not only eradicate primary tumors but will generate systemic antitumor immunity capable of destroying distant metastases. A major problem that must first be surmounted relates to the immune resistance of large tumors. Here we reveal that immune resistance can be overcome by combining immunotherapy with a concerted attack on the tumor vasculature. The functionally related antitumor drugs 5,6-dimethylxanthenone-4-acetic acid (DMXAA) and flavone acetic acid (FAA), which cause tumor vasculature collapse and tumor necrosis, were used to attack the tumor vasculature, whereas the T-cell costimulator B7.1 (CD80), which costimulates T-cell proliferation via the CD28 pathway, was used to stimulate antitumor immunity. The injection of cDNA (60–180 µg) encoding B7.1 into large EL-4 tumors (0.8 cm in diameter) established in C57BL/6 mice, followed 24 h later by i.p. administration of either DMXAA (25 mg/kg) or FAA (300 mg/kg), resulted in complete tumor eradication within 2–6 weeks. In contrast, monotherapies were ineffective. Both vascular attack and B7.1 immunotherapy led to up-regulation of heat shock protein 70 on stressed and dying tumor cells, potentially augmenting immunotherapy. Remarkably, large tumors took on the appearance of a wound that rapidly ameliorated, leaving perfectly healed skin. Combined therapy was mediated by CD8+ T cells and natural killer cells, accompanied by heightened and prolonged antitumor cytolytic activity (P < 0.001), and by a marked increase in tumor cell apoptosis. Cured animals completely rejected a challenge of 1 x 107 parental EL-4 tumor cells but not a challenge of 1 x 104 Lewis lung carcinoma cells, demonstrating that antitumor immunity was tumor specific. Adoptive transfer of 2 x 108 splenocytes from treated mice into recipients bearing established (0.8 cm in diameter) tumors resulted in rapid and complete tumor rejection within 3 weeks. Although DMXAA and B7.1 monotherapies are complicated by a narrow range of effective doses, combined therapy was less dosage dependent. Thus, a broad range of amounts of B7.1 cDNA were effective in combination with 25 mg/kg DMXAA. In contrast, DMXAA, which has a very narrow range of high active doses, was effective at a low dose (18 mg/kg) when administered with a large amount (180 µg) of B7.1 cDNA. Importantly, combinational therapy generated heightened antitumor immunity, such that gene transfer of B7.1 into one tumor, followed by systemic DMXAA treatment, led to the complete rejection of multiple untreated tumor nodules established in the opposing flank. These findings have important implications for the future direction and utility of cancer immunotherapies aimed at harnessing patients’ immune responses to their own tumors.

A medium-temperature solar thermal power system and its efficiency optimisation

This paper firstly expounds that the reheat-regenerative Rankine power cycle is a suitable cycle for the parabolic trough collector, a popular kind of collector in the power industry. In a thermal power cycle, the higher the temperature at which heat is supplied, the higher the efficiency of the cycle. On the other hand, for a given kind of collector at the same exiting temperature, the higher the temperature of the fluid entering the collector, the lower the efficiency of the collector. With the same exiting temperature of the solar field and the same temperature differences at the hottest end of the superheater/reheater and at the pinch points in the heat exchangers (e.g., the boiler) in the cycle, the efficiencies of the system are subject to the temperature of the fluid entering the collector or the saturation temperature at the boiler. This paper also investigates the optimal thermal and exergetic efficiencies for the combined system of the power cycle and collector. To make most advantage of the collector, the exiting fluid is supposed to be at the maximum temperature the collector can harvest. Hence, the thermal and exergetic efficiencies of the system are related to the saturation temperature at the boiler here.

Environmental management system and electronic communication : Is it the need of the hour?

Implementation and certification of Environmental Management Systems (EMS) is a reality for many businesses. Communication with an organisation’s stakeholders is a required element of any EMS. In the last five years companies have steadily moved towards integrating their different management systems, such as quality, environmental, and occupational health and safety, in an attempt to reduce their costs and increase efficiency. Legislation requires extensive reporting in each of these areas, so compliance is another important driver. During this period, communication by digital technology, or electronic communication, has gained prominence and acceptance amongst all groups of people including businesses primarily as a means to disseminate crucial EMS information to geographically diverse employees in a cost effective and instantaneous manner. Some perspectives have emerged to suggest that change processes in organisations may be hindered or helped in various ways through the application of digital technology in EMS. There are, however, gaps in the literature that document the impact and effectiveness of electronic communication amongst EMS stakeholders. In this paper we will discuss employees as one of the major stakeholders and whether the move to electronic communication has been assisting or hindering transformations in awareness and understanding of issues amongst employees. We highlight opportunities and challenges presented by an increased use of electronic communication in light of the environmental and climate change debates, which underpin EMS.

A systematic policy approach to changing the food system and physical activity environments to prevent obesity

As obesity prevention becomes an increasing health priority in many countries, including Australia
and New Zealand, the challenge that governments are now facing is how to adopt a systematic
policy approach to increase healthy eating and regular physical activity. This article sets out a
structure for systematically identifying areas for obesity prevention policy action across the food
system and full range of physical activity environments. Areas amenable to policy intervention can
be systematically identified by considering policy opportunities for each level of governance (local,
state, national, international and organisational) in each sector of the food system (primary
production, food processing, distribution, marketing, retail, catering and food service) and each
sector that influences physical activity environments (infrastructure and planning, education,
employment, transport, sport and recreation). Analysis grids are used to illustrate, in a structured
fashion, the broad array of areas amenable to legal and regulatory intervention across all levels of
governance and all relevant sectors. In the Australian context, potential regulatory policy
intervention areas are widespread throughout the food system, e.g., land-use zoning (primary
production within local government), food safety (food processing within state government), food
labelling (retail within national government). Policy areas for influencing physical activity are
predominantly local and state government responsibilities including, for example, walking and
cycling environments (infrastructure and planning sector) and physical activity education in schools
(education sector). The analysis structure presented in this article provides a tool to systematically
identify policy gaps, barriers and opportunities for obesity prevention, as part of the process of
developing and implementing a comprehensive obesity prevention strategy. It also serves to
highlight the need for a coordinated approach to policy development and implementation across
all levels of government in order to ensure complementary policy action.

Monitoring the performance of a microkernel based operating system and supported applications

The message passing microkernel based operating system is a class of operating system in which the policies are implemented using servers whose co-operation is supported by using a small hardware dependent layer called a microkernel. This thesis addresses the issue of reducing the performance deficiency by documenting the synthesis, development, implementation and assessment of a methodology and mechanisms for monitoring the performance of a message passing microkernel based operating system and supported processes. The methodology has been extensively evaluated to ensure that it can be used successfully to monitor performance.

No evidence of expression of two classes of natural antibiotics (cathelicidins and defensins) in a sample of platypus milk

Marsupial neonates are born without a fully functioning immune system, and are known to be protected in part by natural antimicrobial peptides present in their mother's milk. Monotreme neonates hatch at a similar stage in development, and it has been hypothesised that their survival in a non-sterile burrow also relies on the presence of natural antibiotics in their mother's milk. Here we review the field of monotreme lactation and the antimicrobial peptide complement of the platypus (Ornithorhynchus anatinus). Using reverse transcriptasepolymerase chain reaction of milk cell RNA from a sample of platypus milk, we found no evidence for the expression of cathelicidins or defensins in the milk. This was unexpected. We hypothesise that these natural antibiotics may instead be produced by the young platypuses themselves.