β-glucan triggers spondylarthritis and Crohn's disease-like ileitis in SKG mice

Objective The spondylarthritides (SpA), including ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, and arthritis associated with inflammatory bowel disease, cause chronic inflammation of the large peripheral and axial joints, eyes, skin, ileum, and colon. Genetic studies reveal common candidate genes for AS, PsA, and Crohn's disease, including IL23R, IL12B, STAT3, and CARD9, all of which are associated with interleukin-23 (IL-23) signaling downstream of the dectin 1 β-glucan receptor. In autoimmune-prone SKG mice with mutated ZAP-70, which attenuates T cell receptor signaling and increases the autoreactivity of T cells in the peripheral repertoire, IL-17–dependent inflammatory arthritis developed after dectin 1–mediated fungal infection. This study was undertaken to determine whether SKG mice injected with 1,3-β-glucan (curdlan) develop evidence of SpA, and the relationship of innate and adaptive autoimmunity to this process. Methods SKG mice and control BALB/c mice were injected once with curdlan or mannan. Arthritis was scored weekly, and organs were assessed for pathologic features. Anti–IL-23 monoclonal antibodies were injected into curdlan-treated SKG mice. CD4+ T cells were transferred from curdlan-treated mice to SCID mice, and sera were analyzed for autoantibodies. Results After systemic injection of curdlan, SKG mice developed enthesitis, wrist, ankle, and sacroiliac joint arthritis, dactylitis, plantar fasciitis, vertebral inflammation, ileitis resembling Crohn's disease, and unilateral uveitis. Mannan triggered spondylitis and arthritis. Arthritis and spondylitis were T cell– and IL-23–dependent and were transferable to SCID recipients with CD4+ T cells. SpA was associated with collagen- and proteoglycan-specific autoantibodies. Conclusion Our findings indicate that the SKG ZAP-70W163C mutation predisposes BALB/c mice to SpA, resulting from innate and adaptive autoimmunity, after systemic β-glucan or mannan exposure.

Identifying the triggers for management services in business transformation management

Business transformations are complex organisational change endeavours that result in a business performing current work differently, or performing different work. Information Technology (IT) is a key enabler of such initiatives, but comes with its challenges, as revamping the IT infrastructure in large-scale organisations implies high complexity, high risk, and often high failure rates. We view business transformations as a collection of management services that are demanded and enacted at a program level, defined as abstract resources that provide the managerial capabilities necessary for business transformations. In this research-in-progress, we explore what triggers the need for management services in response to the challenges in business transformation management. We analyse data from two exploratory case studies using the critical incident technique as our qualitative analysis method. Early findings indicate that management service triggers reside on either the strategic level, which may be internally or externally driven, or at the program management level, which may be situational, influential or reactional. We detail implications for our on-going research.

Cellular stress triggers the human topoisomerase I damage response independently of DNA damage in a p53 controlled manner

The 'human topoisomerase I (htopoI) damage response' was reported to be triggered by various kinds of DNA lesions. Also, a high and persistent level of htopoI cleavage complexes correlated with apoptosis. In the present study, we demonstrate that DNA damage-independent induction of cell death using colcemid and tumor necrosis factor is also accompanied by a strong htopoI response that correlates with the onset of apoptotic hallmarks. Consequently, these results suggest that htopoI cleavage complex formation may be caused by signaling pathways independent of the kind of cellular stress. Thus, protein interactions or signaling cascades induced by DNA damage or cellular stress might lead to the formation of stabilized cleavage complexes rather than the DNA lesion itself. Finally, we show that p53 not only plays a key role in the regulation of the htopoI response to UV-C irradiation but also to treatment with colcemid.

Making things happen: How the environment triggers action

Innovative research conducted by Dr Jan Golembiewski from Medical Architectures Australasia-Pacific, in the area of environmental design for mental healthcare helps us reflect, through experiential storytelling, on the importance of paying attention to positive environmental ‘triggers for action’ when designing physical spaces to help manage particular patients’ conditions. This article is written about the mental health experience specifically, however environmental design is an issue we can all relate to in our everyday lives (at home, at work, social spots or in places such as hospitals or retreats) when we instinctively notice a connection between our mental health and our surroundings or a healthy sense of place.

What triggers problem recognition? An exploration on young Australian male problematic online gamers

Help-seeking is a complex decision-making process that first begins with problem recognition. However, little is understood about the conceptualisation of the helpseeking process and the triggers of problem recognition. This research proposes the use of the Critical Incident Technique (CIT) to examine and classify incidents that serve as key triggers of problem recognition among young Australian male problematic online gamers. The research provides a classification of five different types of triggers that will aid social marketers into developing effective early detection, prevention and treatment focused social marketing interventions.

The mechanical triggers of plaque rupture: Shear stress vs pressure gradient

The aim of this study was to evaluate the mechanical triggers that may cause plaque rupture. Wall shear stress (WSS) and pressure gradient are the direct mechanical forces acting on the plaque in a stenotic artery. Their influence on plaque stability is thought to be controversial. This study used a physiologically realistic, pulsatile flow, two-dimensional, cine phase-contrast MRI sequence in a patient with a 70% carotid stenosis. Instead of considering the full patient-specific carotid bifurcation derived from MRI, only the plaque region has been modelled by means of the idealised flow model. WSS reached a local maximum just distal to the stenosis followed by a negative local minimum. A pressure drop across the stenosis was found which varied significantly during systole and diastole. The ratio of the relative importance of WSS and pressure was assessed and was found to be less than 0.07% for all time phases, even at the throat of the stenosis. In conclusion, although the local high WSS at the stenosis may damage the endothelium and fissure plaque, the magnitude of WSS is small compared with the overall loading on plaque. Therefore, pressure may be the main mechanical trigger for plaque rupture and risk stratification using stress analysis of plaque stability may only need to consider the pressure effect.

Recent insights into microbial triggers of interleukin-10 production in the host and the impact on infectious disease pathogenesis

Since its initial description as a Th2-cytokine antagonistic to interferon-alpha and granulocyte-macrophage colony-stimulating factor, many studies have shown various anti-inflammatory actions of interleukin-10 (IL-10), and its role in infection as a key regulator of innate immunity. Studies have shown that IL-10 induced in response to microorganisms and their products plays a central role in shaping pathogenesis. IL-10 appears to function as both sword and shield in the response to varied groups of microorganisms in its capacity to mediate protective immunity against some organisms but increase susceptibility to other infections. The nature of IL-10 as a pleiotropic modulator of host responses to microorganisms is explained, in part, by its potent and varied effects on different immune effector cells which influence antimicrobial activity. A new understanding of how microorganisms trigger IL-10 responses is emerging, along with recent discoveries of how IL-10 produced during disease might be harnessed for better protective or therapeutic strategies. In this review, we summarize studies from the past 5 years that have reported the induction of IL-10 by different classes of pathogenic microorganisms, including protozoa, nematodes, fungi, viruses and bacteria and discuss the impact of this induction on the persistence and/or clearance of microorganisms in the host.

Making and changing wills: Prevalence, predictors, and triggers

Wills are important social, economic, and legal documents. Yet little is known about current will making practices and intentions. A comprehensive national database on the prevalence of will making in Australia was developed to identify who is or is not most likely to draw up a will and triggers for making and changing wills. A national survey of 2,405 adults aged above 18 years was administered by telephone in August and September 2012. Fifty-nine percent of the Australian adult population has a valid will, and the likelihood of will making increases with age and estate value. Efforts to get organized, especially in combination with life stage and asset changes trigger will making; procrastination, rather than a strong resistance, appears to explain not making a will. Understanding will making is timely in the context of predicted significant intergenerational transfers of wealth, changing demographics, and a renewed emphasis on retirement planning.

Trehalose accumulation triggers autophagy during plant desiccation

Global climate change, increasingly erratic weather and a burgeoning global population are significant threats to the sustainability of future crop production. There is an urgent need for the development of robust measures that enable crops to withstand the uncertainty of climate change whilst still producing maximum yields. Resurrection plants possess the unique ability to withstand desiccation for prolonged periods, can be restored upon watering and represent great potential for the development of stress tolerant crops. Here, we describe the remarkable stress characteristics of Tripogon loliiformis, an uncharacterised resurrection grass and close relative of the economically important cereals, rice, sorghum, and maize. We show that T. loliiformis survives extreme environmental stress by implementing autophagy to prevent Programmed Cell Death. Notably, we identified a novel role for trehalose in the regulation of autophagy in T.loliiformis. Transcriptome, Gas Chromatography Mass Spectrometry, immunoblotting and confocal microscopy analyses directly linked the accumulation of trehalose with the onset of autophagy in dehydrating and desiccated T. loliiformis shoots. These results were supported in vitro with the observation of autophagosomes in trehalose treated T. loliiformis leaves; autophagosomes were not detected in untreated samples. Presumably, once induced, autophagy promotes desiccation tolerance in T.loliiformis , by removal of cellular toxins to suppress programmed cell death and the recycling of nutrients to delay the onset of senescence. These findings illustrate how resurrection plants manipulate sugar metabolism to promote desiccation tolerance and may provide candidate genes that are potentially useful for the development of stress tolerant crops.

Extreme sports as a facilitator of ecocentricity and positive life changes

Extreme sports and extreme sports participants have been most commonly explored from a negative perspective, for example the 'need to take unnecessary risks'. This study reports on findings that indicate a more positive experience. A phenomenological method was used via unstructured interviews with 15 extreme sports participants and other first hand accounts. The extreme sports included B.A.S.E. jumping, big wave surfing, extreme skiing, waterfall kayaking, extreme mountaineering and solo rope-free climbing. Results indicate that participating in activities that involve a real chance of death, fear and the realisation that nature in its extreme is far greater and more powerful than humanity triggers positive life changes, and an eco-centric standpoint.

Keeping giving going : charitable bequests and Australians

The potential of bequests to contribute to the sustainability of charities1 is immense, with social and economic trends opening up the bequest landscape. Yet so much is unknown about how Australians think about charitable bequests – particularly about the motivations, barriers and triggers surrounding this behaviour. Do bequestors differ from other donors? What prevents good intentions from becoming good actions? Where do charities figure in this process? This study aims at a better understanding of those Australians who make a charitable bequest and those who might. It offers individual charities, and the sector as a whole, empirical evidence to support and extend the anecdotal knowledge of those working with donors around this sensitive, but vital, area. This research has been supported by the Perpetual Foundation, the EF and SL Gluyas Trust and the Edward Corbould Charitable Trust under the management of Perpetual Trustee Company Ltd.

Analysing the internationalisation readiness of firms

The internationalisation of firms has gained much research attention since the 1970s. However, the behavioural aspect of firms’ during their pre-internationalisation phase has not been sufficiently explored. This research proposes that a pre-internationalisation focus would not only offer an additional perspective to the study of firm internationalisation but would also address the significant research gap in studies that are theoretically based around the Uppsala Model. This study views the development of a firm from its pre-internationalisation phase into an international firm in accordance with the Uppsala Model’s ‘state’ to ‘change’ aspect transition, with ‘internationalisation readiness’ established as the missing link between these two aspects. During the pre-internationalisation phase, a firm is exposed to a wide variety of internal and external stimuli that triggers an impulse for foreign market expansion. The perception of these stimuli and the attitudinal commitment taken by the firm’s decision-makers, as well as the firm’s resource capabilities and the moderating effect of lateral rigidity, are influential towards an internationalisation decision. This paper argues the significance of adopting the pre-internationalisation phase as a research platform and the importance of analysing firms’ internationalisation readiness. A method is proposed for the development of an Internationalisation Readiness Index that could be used for measuring a firm’s propensity to commence its first export operation.

Age-related maculopathy : linking aetiology and pathophysiological changes to the ischaemia hypothesis

Age-related maculopathy (ARM) has remained a challenging topic with respect to its aetiology, pathomechanisms, early detection and treatment since the late 19th century when it was first described as its own entity. ARM was previously considered an inflammatory disease, a degenerative disease, a tumor and as the result of choroidal hemodynamic disturbances and ischaemia. The latter processes have been repeatedly suggested to have a key role in its development and progression. In vivo experiments under hypoxic conditions could be models for the ischaemic deficits in ARM. Recent research has also linked ARM with gene polymorphisms. It is however unclear what triggers a person's gene susceptibility. In this manuscript, a linking hypothesis between aetiological factors including ischaemia and genetics and the development of early clinicopathological changes in ARM is proposed. New clinical psychophysical and electrophysiological tests are introduced that can detect ARM at an early stage. Models of early ARM based upon hemodynamic, photoreceptor and post-receptoral deficits are described and the mechanisms by which ischaemia may be involved as a final common pathway are considered. In neovascular age-related macular degeneration (neovascular AMD), ischaemia is thought to promote release of vascular endothelial growth factor (VEGF) which induces chorioretinal neovascularisation. VEGF is critical in the maintenance of the healthy choriocapillaris. In the final section of the manuscript the documentation of the effect of new anti-VEGF treatments on retinal function in neovascular AMD is critically viewed.

Why adopt now? Multiple case studies and survey studies comparing small, medium and large firms

While a number of factors have been highlighted in the innovation adoption literature, little is known about the key triggers of innovation adoption across differently-sized firms. This study compares case studies of small, medium and large manufacturing firms who recently decided to adopt a process innovation. We also employ organizational surveys from 134 firms investigating the factors which influence innovation adoption. The quantitative results support the qualitative findings that the external pressures are a trigger among small to medium firms, while the larger firm’s adoption was associated with internal causes.