Simultaneous neuroprotection and blockade of inflammation reverses autoimmune encephalomyelitis

In multiple sclerosis, the immune system attacks the white matter of the brain and spinal cord, leading to disability and/or paralysis. Myelin, oligodendrocytes and neurons are lost due to the release by immune cells of cytotoxic cytokines, autoantibodies and toxic amounts of the excitatory neurotransmitter glutamate. Experimental autoimmune encephalomyelitis (EAE) is an animal model that exhibits the clinical and pathological features of multiple sclerosis. Current therapies that suppress either the inflammation or glutamate excitotoxicity are partially effective when administered at an early stage of EAE, but cannot block advanced disease. In a multi-faceted approach to combat EAE, we blocked inflammation with an anti-MAdCAM-1 (mucosal addressin cell adhesion molecule-1) monoclonal antibody and simultaneously protected oligodendrocytes and neurons against glutamate-mediated damage with the -amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate antagonist 2,3-dihydroxy-6-nitro-7- sulfamoylbenzo(f)quinoxaline (NBQX) and the neuroprotector glycine–proline–glutamic acid (GPE; N-terminal tripeptide of insulin-like growth factor). Remarkably, administration at an advanced stage of unremitting EAE of either a combination of NBQX and GPE, or preferably all three latter reagents, resulted in amelioration of disease and repair of the CNS, as assessed by increased oligodendrocyte survival and remyelination, and corresponding decreased paralysis, inflammation, CNS apoptosis and axonal damage. Each treatment reduced the expression of nitric oxide and a large panel of proinflammatory and immunoregulatory cytokines, in particular IL-6 which plays a critical role in mediating EAE. Mice displayed discernible improvements in all physical features examined. Disease was suppressed for 5 weeks, but relapsed when treatment was suspended, suggesting treatment must be maintained to be effective. The above approaches, which allow CNS repair by inhibiting inflammation and/or simultaneously protect neurons and oligodendrocytes from damage, could thus be effective therapies for multiple sclerosis.

Basic symptoms in young people at ultra high-risk of psychosis

Basic Symptoms are cognitive and emotional disturbances characteristic of the early stage of psychosis. This study established the utility of an instrument to identify Basic Symptoms amongst young people at high-risk for developing psychosis, thereby facilitating the pathway to treatment for these individuals. The portfolio focuses on how having an unwell parent contributes to and influences the development of psychopathology in offspring. The four clinical case studies are presented in detail, and the intervention strategies for each individual are evaluated.

Violent offender rehabilitation and the therapeutic community model of treatment : towards integrated service provision?

Rehabilitation programs for violent offenders are at an early stage in their development, and there is currently only a very limited empirical base from which to draw any conclusions about treatment effectiveness (Jolliffe and Farrington, 2007). Therapeutic communities for offender populations have a much longer history, although the effects of applying this model of treatment to violent offenders have not been systematically investigated. This paper reviews the content and evidence supporting both violent offender treatment programs and therapeutic community models, concluding that approaches to treatment which combine features of both may prove to be most successful, and warrant further development and evaluation.

Customer-product interaction : a model for new product development in entrepreneurial firms

Use of New Product Development (NPD) methods may benefit New Zealand SMEs and entrepreneurial firms in gaining greater market share. In this paper we review the literature on New Product Development, NPD theory and methods for early stage product design and development. Our reading suggests that product design has greater success when the customer is involved in the design effort. It also recommends methods of approach to new markets in the (NPD) life cycle. The literature further elucidates methods for identification of product design criteria based on customer needs identification. In essence, customer-product interaction in the early stages of product development is important to product success in new markets for entrepreneurial firms and SMEs. Of particular interest are early-stage NPD research methods and their influence on the company’s marketing strategy.

The efficacy of partnership evaluation and its impact on alliance transformation : a case study 12 months post evaluation

Partnerships involving higher education, governments, and industry have been recognised as important vehicles for engaging community, leveraging knowledge, and sharing potential resources. The critical need for these partnerships in rural and regional locations has been of particular note. Partnership evaluation can serve a critical function of informing continuous improvement and may therefore assist the evaluated agencies to work towards responsive transformational change. The ability for a partnership to adapt and change may aid in their sustainability. Despite the potentially important role of partnership evaluation, the development of tools that measure partnership are at an early stage. Partnership evaluation is rarely reflected upon in the published literature. Moreover, benefits and reflections of the efficacy of evaluations 12 months post analysis is rare in the published literature. Therefore, a brief review of partnership approaches and measurement tools are presented. The purpose of this paper is to reflect upon the efficacy of an evaluation conducted 12 months previously of a partnership between Deakin University, the Department of Health and Department of Human Services (Barwon South West Region), known as the Deakin/DH/DHS Strategic Alliance. This case study reviews several tools/metrics utilised. The efficacy of the evaluation tools is discussed. Those metrics, underlying the tools which contributed to positive change in partnerships are discussed.

In-situ confocal Raman monitoring of evaporation process during protein crystallization

We have introduced an in-situ Raman monitoring technique to investigate the crystallization process inside protein drops. In addition to a conventional vapour-diffusion process, a novel procedure which actively stimulates the evaporation from a protein drop during crystallization was also evaluated, with lysozyme as a model protein. In contrast to the conventional vapour-diffusion condition, the evaporation-stimulated growth of crystals was initiated in a simple dehydration scheme and completed within a significantly shorter time. To gain an understanding of crystallization behaviours under the conditions with and without such evaporation stimulation, confocal Raman spectroscopy combined with linear regression analysis was used to monitor both lysozyme and HEPES buffer concentrations in real time. The confocal measurements having a high spatial resolution and good linear response revealed areas of local inhomogeneity in protein concentration when the crystallization started. The acquired concentration profiles indicated that (1)ÿthe evaporation-stimulated crystallization proceeded with protein concentrations lower than those under conventional vapour diffusion, and (2)ÿcrystals under the evaporation-stimulated condition were noticeable within an early stage of crystallization before the protein concentration approached its maximum value. The HEPES concentration profiles, on the other hand, increased steadily towards the end of the process regardless of the conditions used for crystallization. In particular, the observed local inhomogeneities specific to protein distribution suggested an accumulation mechanism of protein molecules that initiates the nucleation of crystals.

Genetic control of male fertility in Arabidopsis thaliana : structural analysis of premeiotic developmental mutants

We have taken a mutational approach to identify genes important for male fertility in Arabidopsis thaliana and have isolated a number of nuclear male/ sterile mutants in which vegetative growth and female fertility are not altered. Here we describe detailed developmental analyses of four mutants, each of which defines a complementation group and has a distinct developmental end point. All four mutants represent premeiotic developmental lesions. In ms3, tapetum and middle layer hypertrophy result in the degeneration of microsporocytes. In ms4, microspore dyads persist for most of anther development as a result of impaired meiotic division. In ms5, degeneration occurs in all anther cells at an early stage of development. In ms15, both the tapetum and microsporocytes degenerate early in anther development. Each of these mutants had shorter filaments and a greater number of inflorescences than congenic male-fertile plants. The differences in the developmental phenotypes of these mutants, together with the non-allelic nature of the mutations indicate that four different genes important for pollen development, have been identified.

Occupant interaction with interior environment in Greek dwellings during summer

User behaviour significantly affects energy consumption simulation estimates, which can consequently influence architectural design decisions at an early stage. Different regional behavioural patterns could, therefore, hinder the applicability of certain architectural and environmental strategies. Through questionnaires analysis and field studies, this study investigates the pattern use of manual control of windows, shading and air condition units, in residential buildings in Greece, during summer. Initial findings of the analysis indicate significant interaction of Greek residents with the building shell, in their effort to maintain comfort.

Optimising the life cycle energy performance of residential buildings

A holistic approach to low-energy building design is essential to ensure that any efficiency improvement strategies provide a net energy benefit over the life of the building. Previous work by the authors has established a model for informing low-energy building design based on a comparison of the life cycle energy demand associated with a broad range of building assemblies. This model ranks assemblies based on their combined initial and recurrent embodied energy and operational energy demand. The current study applies this model to an actual residential building in order to demonstrate the application of the model for optimising a building’s life cycle energy performance. The aim of this study was to demonstrate how the availability of comparable energy performance information at the building design stage can be used to better optimise a building’s energy performance. The life cycle energy demand of the case study building, located in the temperate climate of Melbourne, Australia, was quantified using a comprehensive embodied energy assessment technique and TRNSYS thermal energy simulation software. The building was then modelled with variations to its external assemblies in an attempt to optimise its life cycle energy performance. The alternative assemblies chosen were those shown through the author’s previous modelling to result in the lowest life cycle energy demand for each building element. The best performing assemblies for each of the main external building elements were then combined into a best-case scenario to quantify the potential life cycle energy savings possible compared to the original building. The study showed that significant life cycle energy savings are possible through the modelling of individual building elements for the case study building. While these findings relate to a very specific case, this study demonstrates the application of a model for optimising building life cycle energy performance that may be applied more broadly during early-stage building design to optimise life cycle energy performance.

Electrospinning of nanofibres with parallel line surface texture for improvement of nerve cell growth

Nanofibres having a parallel line surface texture were electrospun from cellulose acetate butyrate solutions using a solvent mixture of acetone and N,N'-dimethylacetamide. The formation mechanism of the unusual surface feature was explored and attributed to the formation of voids on the jet surface at the early stage of electrospinning and subsequent elongation and solidification of the voids into a line surface structure. The fast evaporation of a highly volatile solvent, acetone, from the polymer solution was found to play a key role in the formation of surface voids, while the high viscosity of the residual solution after the solvent evaporation ensured the line surface to be maintained after the solidification. Based on this principle, nanofibres having a similar surface texture were also electrospun successfully from other polymers, such as cellulose acetate, polyvinylidene fluoride, poly(methyl methacrylate), polystyrene and poly(vinylidene fluoride-co-hexafluoropropene), either from the same or from different solvent systems. Polarized Fourier transform infrared spectroscopy was used to measure the polymer molecular orientation within nanofibres. Schwann cells were grown on both aligned and randomly oriented nanofibre mats. The parallel line surface texture assisted in the growth of Schwann cells especially at the early stage of cell culture regardless of the fibre orientation. In contrast, the molecular orientation within nanofibres showed little impact on the cell growth.

Needleless eletrospinning of polystyrene fibers with an oriented surface line texture

We have demonstrated that polystyrene (PS) nanofibers having an ordered surface line texture can be produced on a large scale from a PS solution of acetone and N,N′-dimethylformamide (2/1, vol/vol) by a needleless electrospinning technique using a disc as fiber generator. The formation of the unusual surface feature was investigated and attributed to the voids formed on the surface of jets due to the fast evaporation of acetone at the early stage of electrospinning, and subsequent elongation and solidification turning the voids into ordered lines on fiber surface. In comparison with the nanofibers electrospun by a conventional needle electrospinning using the same solution, the disc electrospun fibers were finer with similar diameter distribution. The fiber production rate for the disc electrospinning was 62 times higher than that of the conventional electrospinning. Fourier transform infrared spectroscopy and X-ray diffraction measurements indicated that the PS nanofibers produced from the two electrospinning techniques showed no significant difference in chemical component, albeit slightly higher crystallinity in the disc spun nanofibers.

X4 and R5 HIV-1 have distinct post-entry requirements for uracil DNA glycosylase during infection of primary cells

It has been assumed that R5 and X4 HIV utilize similar strategies to support viral cDNA synthesis post viral entry. In this study, we provide evidence to show that R5 and X4 HIV have distinct requirements for host cell uracil DNA glycosylase (UNG2) during the early stage of infection. UNG2 has been previously implicated in HIV infection, but its precise role remains controversial. In this study we show that, although UNG2 is highly expressed in different cell lines, UNG2 levels are low in the natural host cells of HIV. Short interfering RNA knockdown of endogenous UNG2 in primary cells showed that UNG2 is required for R5 but not X4 HIV infection and that this requirement is bypassed when HIV enters the target cell via vesicular stomatitis virus envelope-glycoprotein-mediated endocytosis. We also show that short interfering RNA knockdown of UNG2 in virus-producing primary cells leads to defective R5 HIV virions that are unable to complete viral cDNA synthesis. Quantitative PCR analysis revealed that endogenous UNG2 levels are transiently up-regulated post HIV infection, and this increase in UNG2 mRNA is ∼10–20 times higher in R5 versus X4 HIV-infected cells. Our data show that both virion-associated UNG2 and HIV infection-induced UNG2 expression are critical for reverse transcription during R5 but not X4 HIV infection. More importantly, we have made the novel observation that R5 and X4 HIV have distinct host cell factor requirements and differential capacities to induce gene expression during the early stages of infection. These differences may result from activation of distinct signaling cascades and/or infection of divergent T-lymphocyte subpopulations.

Clostridial spores for cancer therapy : targeting solid tumour microenvironment

Solid tumour accounts for 90% of all cancers. The current treatment approach for most solid tumours is surgery, however it is limited to early stage tumours. Other treatment options such as chemotherapy and radiotherapy are non-selective, thus causing damage to both healthy and cancerous tissue. Past research has focused on understanding tumour cells themselves, and conventional wisdom has aimed at targeting these cells directly. Recent research has shifted towards understanding the tumour microenvironment and it’s differences from that of healthy cells/tissues in the body and then to exploit these differences for treatmeat of the tumour. One such approach is utilizing anaerobic bacteria. Several strains of bacteria have been shown to selectively colonize in solid tumours, making them valuable tools for selective tumour targeting and destruction. Amongst them, the anaerobic Clostridium has shown great potential in penetration and colonization of the hypoxic and necrotic areas of the tumour microenvironment, causing significant oncolysis as well as enabling the delivery of therapeutics directly to the tumour in situ. Various strategies utilizing Clostridium are currently being investigated, and represent a novel area of emerging cancer therapy. This review provides an update review of tumour microenvironment as well as summary of the progresses and current status of Clostridial spore-based cancer therapies.

Establishment and development of a seabird colony : long-term trends in phenology, breeding success, recruitment, breeding density and demography

Few studies document long-term colony-level metrics from colony establishment to maturity (equilibrium) and few test predictions of general models of colony development. We describe long-term trends in a colony of Australasian Gannets (Morus serrator) which has been monitored from an early stage in its development. The colony at Pope’s Eye, within Port Phillip Bay, Victoria, Australia was established in 1984 on an artificial structure and the first nest count (25 nests) was conducted in the same year. The colony was then studied for 15 of 19 years between 1988 and 2006–2007. During the study, 2,516 eggs were recorded, resulting in 1,694 chicks hatching (67 % of eggs), of which 1,310 (77 % of those hatched) fledged. At least 184 (14 %) of fledged offspring returned to Pope’s Eye as breeding adults. Since establishment, the number and density of nests increased (number of nests increased 8.8 % annually), with density increasing at varying rates in different areas of the colony. Early recruitment involved birds from a nearby colony, but within 5 years post establishment the first natal recruits were breeding at Pope’s Eye and thereafter natal recruitment was the main source of new breeding adults (totalling 81.4 % of all recruits). Age of recruitment varied throughout the study, though not systematically, and there was no difference between the sexes. The pattern of rapid initial growth is typical of patterns reported for other seabird colonies. However, as the colony (and birds within it) aged, there was no increase in breeding success and egg laying did not become earlier, as was expected from general models of colony development.

Recording Australian animation history

Animation has been practised in Australia from a relatively early stage in the worldwide history of cinematic animation, as evidenced by quite mature examples of cutout animation by cartoonist Harry Julius beginning in 1912. It may therefore seem odd that there is comparatively little written of its history. In America and Europe established histories of animation have been recorded. The growth of the medium in these other countries led to the comparatively early establishment of institutions teaching its history and practice.