Cholesterol regulates Syntaxin 6 trafficking at trans-Golgi network endosomal boundaries.

Inhibition of cholesterol export from late endosomes causes cellular cholesterol imbalance, including cholesterol depletion in the trans-Golgi network (TGN). Here, using Chinese hamster ovary (CHO) Niemann-Pick type C1 (NPC1) mutant cell lines and human NPC1 mutant fibroblasts, we show that altered cholesterol levels at the TGN/endosome boundaries trigger Syntaxin 6 (Stx6) accumulation into VAMP3, transferrin, and Rab11-positive recycling endosomes (REs). This increases Stx6/VAMP3 interaction and interferes with the recycling of αVβ3 and α5β1 integrins and cell migration, possibly in a Stx6-dependent manner. In NPC1 mutant cells, restoration of cholesterol levels in the TGN, but not inhibition of VAMP3, restores the steady-state localization of Stx6 in the TGN. Furthermore, elevation of RE cholesterol is associated with increased amounts of Stx6 in RE. Hence, the fine-tuning of cholesterol levels at the TGN-RE boundaries together with a subset of cholesterol-sensitive SNARE proteins may play a regulatory role in cell migration and invasion.

Global start-ups profile : one size fits all?

Our research aims to answer the research questions “How do we commonly describe the global start-ups profile as evidenced in prior inductive research?” and “Does this global start-ups profile can effectively explain phenomena in Australian global start-up firms?” We systematically review 29 global start-ups (144 firms) qualitative articles to understand descriptive definitions of global-startup firms. We then triangulate this finding with an Australian high-tech firm. Our contribution is to form a descriptive profile of global start-up phenomenon and raise interesting issues that have potentially fruitful findings for both research and practice. This profile might well be just a deviant from the traditional model that describes how firms establish their footprints, first in their domestic markets followed by moves into cross-border activities. Regardless, government agencies, consultants, and entrepreneurs need to understand the phenomenon. Thus we anticipate that this phenomenon will continue to provide interesting issues for pursuit, both by researchers as well as the practitioner community.

Pituitary tumours : all silent on the epigenetics front

Investigation of the epigenome of sporadic pituitary tumours is providing a more detailed understanding of aberrations that characterise this tumour type. Early studies, in this and other tumour types adopted candidate-gene approaches to characterise CpG island methylation as a mechanism responsible for or associated with gene silencing. However, more recently, investigators have adopted approaches that do not require a priori knowledge of the gene and transcript, as example differential display techniques, and also genome-wide, array-based approaches, to 'uncover' or 'unmask' silenced genes. Furthermore, through use of chromatin immunoprecipitation as a selective enrichment technique; we are now beginning to identify modifications that target the underlying histones themselves and that have roles in gene-silencing events. Collectively, these studies provided convincing evidence that change to the tumour epigenome are not simply epiphenomena but have functional consequences in the context of pituitary tumour evolution. Our ability to perform these types of studies has been and is increasingly reliant upon technological advances in the genomics and epigenomics arena. In this context, other more recent advances and developing technologies, and, in particular, next generation or flow cell re-sequencing techniques offer exciting opportunities for our future studies of this tumour type.

Powering a curriculum for all : a critical ethnographic study of inclusive education

This project makes a contribution to knowledge about the successful leadership practices that enhance education for young people with a disability in a Queensland Secondary School. The project used a critical ethnographic approach with a variety of data collection methods and analysis. For example, the use of work diaries, semi-structured interviews, document analysis and observation. These leadership practices were found to be relevant to the development of inclusive schools for all learners.The most powerful leadership practices found were those used by the leader to challenge, interupt and replace exsisting discourse and processes that led to exclusion of students with a disability.

‘It's all scientific to me’ : focus group insights into why young people do not apply safe-sex knowledge

Despite rising levels of safe-sex knowledge in Australia, sexually transmitted infection notifications continue to increase. A culture-centred approach suggests it is useful in attempting to reach a target population first to understand their perspective on the issues. Twenty focus groups were conducted with 89 young people between the ages of 14 and 16 years. Key findings suggest that scientific information does not articulate closely with everyday practice, that young people get the message that sex is bad and they should not be preparing for it and that it is not appropriate to talk about sex. Understanding how young people think about these issues is particularly important because the focus groups also found that young people disengage from sources of information that do not match their own experiences.

All the Flavours of Asia

A travel article about food and landscape in Thailand. Thick forest islands the first limestone karst that we see. In the cracks and ledges of these cliff faces, low trees make a steady ascent. From the road, it looks an impossible climb, but the forest has managed to find a line to the top and to form a platform of dense canopy. We’re coming into Krabi, an area of southern Thailand famous for these formations. Soon, the forest base will be replaced by ocean. Grottos, undercuts, and yellow beaches will add a skirt of luxury to the drama to the cliffs...

Authentic in all caps

AUTHENTIC IN ALL CAPS is an award-winning web audio adventure for the iPad and Chrome browser. The app combines audio drama, audio tours, and online storytelling. You travel across the web with characters who face ridiculous obstacles to being themselves. It's about identity, mortality, and pizza toppings. It's an audio drama for people who live on the Internet.

Identification of genes important for growth of asymptomatic bacteriuria Escherichia coli in urine

Escherichia coli is the most important etiological agent of urinary tract infections (UTIs). Unlike uropathogenic E. coli, which causes symptomatic infections, asymptomatic bacteriuria (ABU) E. coli strains typically lack essential virulence factors and colonize the bladder in the absence of symptoms. While ABU E. coli can persist in the bladder for long periods of time, little is known about the genetic determinants required for its growth and fitness in urine. To identify such genes, we have employed a transposon mutagenesis approach using the prototypic ABU E. coli strain 83972 and the clinical ABU E. coli strain VR89. Six genes involved in the biosynthesis of various amino acids and nucleobases were identified (carB, argE, argC, purA, metE, and ilvC), and site-specific mutants were subsequently constructed in E. coli 83972 and E. coli VR89 for each of these genes. In all cases, these mutants exhibited reduced growth rates and final cell densities in human urine. The growth defects could be complemented in trans as well as by supplementation with the appropriate amino acid or nucleobase. When assessed in vivo in a mouse model, E. coli 83972carAB and 83972argC showed a significantly reduced competitive advantage in the bladder and/or kidney during coinoculation experiments with the parent strain, whereas 83972metE and 83972ilvC did not. Taken together, our data have identified several biosynthesis pathways as new important fitness factors associated with the growth of ABU E. coli in human urine.

A distributed computing framework for all-to-all comparison problems

Distributed computation and storage have been widely used for processing of big data sets. For many big data problems, with the size of data growing rapidly, the distribution of computing tasks and related data can affect the performance of the computing system greatly. In this paper, a distributed computing framework is presented for high performance computing of All-to-All Comparison Problems. A data distribution strategy is embedded in the framework for reduced storage space and balanced computing load. Experiments are conducted to demonstrate the effectiveness of the developed approach. They have shown that about 88% of the ideal performance capacity have be achieved in multiple machines through using the approach presented in this paper.

High performance all-carbon thin film supercapacitors

We fabricated high performance supercapacitors by using all carbon electrodes, with volume energy in the order of 10−3 Whcm−3, comparable to Li-ion batteries, and power densities in the range of 10 Wcm−3, better than laser-scribed-graphene supercapacitors. All-carbon supercapacitor electrodes are made by solution processing and filtering electrochemically-exfoliated graphene sheets mixed with clusters of spontaneously entangled multiwall carbon nanotubes. We maximize the capacitance by using a 1:1 weight ratio of graphene to multi-wall carbon nanotubes and by controlling their packing in the electrode film so as to maximize accessible surface and further enhance the charge collection. This electrode is transferred onto a plastic-paper-supported double-wall carbon nanotube film used as current collector. These all-carbon thin films are combined with plastic paper and gelled electrolyte to produce solid-state bendable thin film supercapacitors. We assembled supercapacitor cells in series in a planar configuration to increase the operating voltage and find that the shape of our supercapacitor film strongly affects its capacitance. An in-line superposition of rectangular sheets is superior to a cross superposition in maintaining high capacitance when subject to fast charge/discharge cycles. The effect is explained by addressing the mechanism of ion diffusion into stacked graphene sheets.

A sensitivity analysis of train speed and its effect on railway capacity

Increasing train speeds is conceptually a simple and straight forward method to expand railway capacity, for example in comparison to other more extensive and elaborate alternatives. In this article an analytical capacity model has been investigated as a means of performing a sensitivity analysis of train speeds. The results of this sensitivity analysis can help improve the operation of this railway system and to help it cope with additional demands in the future. To test our approach a case study of the Rah Ahane Iran (RAI) national railway network has been selected. The absolute capacity levels for this railway network have been determined and the analysis shows that increasing trains speeds may not be entirely cost effective in all circumstances.

Can’t we all just get along? A qualitative investigation of the cognitive processes motivating driver aggression.

Although driver aggression has been identified as contributing to crashes, current understanding of the fundamental causes of the behaviour is poor. Two key reasons for this are evident. Firstly, existing research has been largely atheoretical, with no unifying conceptual framework guiding investigation. Secondly, emphasis on observable behaviours has resulted in limited knowledge of the underlying thought processes that motivate behaviour. Since driving is fundamentally a social situation, requiring drivers to interpret on-road events, insight regarding these perception and appraisal processes is paramount in advancing understanding of the underlying causes. Thus, the current study aimed to explore the cognitive appraisal processes involved in driver aggression, using a conceptual model founded on the General Aggression Model (Anderson & Bushman, 2002). The present results reflect the first of several studies testing this model. Participants completed 3 structured driving diaries to explore perceptions and cognitions. Thematic analysis of diaries identified several cognitive themes. The first, ‘driving etiquette’ concerned an implied code of awareness and consideration for other motorists, breaches of which were strongly associated with reports of anger and frustration. Such breaches were considered intentional; attributed to dispositional traits of another driver, and precipitated the second theme, ‘justified retaliation’. This theme showed that drivers view their aggressive behaviour as warranted, to convey criticism towards another motorist’s etiquette violation. However, the third theme, ‘superiority’ suggested that those refraining from an aggressive response were motivated by a desire to perceive themselves as ‘better’ than the offending motorists. Collectively, the themes indicate deep-seated and complex thought patterns underlying driver aggression, and suggest the behaviour will be challenging to modify. Implications of these themes in relation to the proposed model will be discussed, and continued research will explore these cognitive processes further, to examine their interaction with person-related factors.