Potential role of EPB41L3 (Protein 4.1B/Dal-1) as a target for treatment of advanced prostate cancer

Background: Loss of erythrocyte membrane protein band 4.1-like 3 (EPB41L3; aliases: protein 4.1B, differentially expressed in adenocarcinoma of the lung-1 (Dal-1)) expression has been implicated in tumor progression. Objective: To evaluate literature describing the role of EPB41L3 in tumorigenesis and metastasis, and to consider whether targeting this gene would be useful in the treatment of prostate cancer. Methods: A literature review of studies describing EPB41L3 and its aliases was conducted. Online databases (NCBI, SwissProt) were also interrogated to collect further data. Results/conclusion: A growing body of evidence supports a role for loss of EPB41L3 in tumor progression, including in prostate cancer. Therapeutic strategies that could be harnessed to upregulate EPB41L3 gene expression in prostate cancer cells are currently being developed.

Addressing factory needs in cane variety selection

Cane fibre content has increased over the past ten years. Some of that increase can be attributed to new varieties selected for release. This paper reviews the existing methods for quantifying the fibre characteristics of a variety, including fibre content and fibre quality measurements – shear strength, impact resistance and short fibre content. The variety selection process is presented and it is reported that fibre content has zero weighting in the current selection index. An updated variety selection approach is proposed, potentially replacing the existing selection process relating to fibre. This alternative approach involves the use of a more complex mill area level model that accounts for harvesting, transport and processing equipment, taking into account capacity, efficiency and operational impacts, along with the end use for the bagasse. The approach will ultimately determine a net economic value for the variety. The methodology lends itself to a determination of the fibre properties that have a significant impact on the economic value so that variety tests can better target the critical properties. A low-pressure compression test is proposed as a good test to provide an assessment of the impact of a variety on milling capacity. NIR methodology is proposed as a technology to lead to a more rapid assessment of fibre properties, and hence the opportunity to more comprehensively test for fibre impacts at an earlier stage of variety development.

Co-branding strategies for luxury fashion brands : Missoni for Target

Missoni is a luxury Italian knitwear brand that partnered with Target in September 2011 releasing a large, one off, mass-market collection that ranged from apparel to home wares. The collaboration received extensive media coverage and was consequently extremely sought after. The online sales site crashed within hours of opening while shelves were cleared in stores minutes after trading began. Within hours more than 40000 items from the collection were posted for sale online at greatly inflated prices. Evaluation of the case study revealed that sales of the Missoni collection increased following the collaboration and the value of the publicity generated at estimated US$100 million. The lack of available stock, despite the enormous hype created, reinforced Missoni’s luxury image. Missoni was able to gain massive awareness of the brand despite not employing any of its own communication channels in the promotion of the collaboration. However the co-branded collaboration was distinctively Missoni, potentially inciting comparison and confusion with the signature line. Nevertheless, this study shows that co-branding strategies can offer a viable opportunity for luxury brands to increase their market share, while they maintain their market position.

Stepping accuracy and visuomotor control among older adults : effect of target contrast and refractive blur

Purpose: Older adults have increased visual impairment, including refractive blur from presbyopic multifocal spectacle corrections, and are less able to extract visual information from the environment to plan and execute appropriate stepping actions; these factors may collectively contribute to their higher risk of falls. The aim of this study was to examine the effect of refractive blur and target visibility on the stepping accuracy and visuomotor stepping strategies of older adults during a precision stepping task. Methods: Ten healthy, visually normal older adults (mean age 69.4 ± 5.2 years) walked up and down a 20 m indoor corridor stepping onto selected high and low-contrast targets while viewing under three visual conditions: best-corrected vision, +2.00 DS and +3.00 DS blur; the order of blur conditions was randomised between participants. Stepping accuracy and gaze behaviours were recorded using an eyetracker and a secondary hand-held camera. Results: Older adults made significantly more stepping errors with increasing levels of blur, particularly exhibiting under-stepping (stepping more posteriorly) onto the targets (p<0.05), while visuomotor stepping strategies did not significantly alter. Stepping errors were also significantly greater for the low compared to the high contrast targets and differences in visuomotor stepping strategies were found, including increased duration of gaze and increased interval between gaze onset and initiation of the leg swing when stepping onto the low contrast targets. Conclusions: These findings highlight that stepping accuracy is reduced for low visibility targets, and for high levels of refractive blur at levels typically present in multifocal spectacle corrections, despite significant changes in some of the visuomotor stepping strategies. These findings highlight the importance of maximising the contrast of objects in the environment, and may help explain why older adults wearing multifocal spectacle corrections exhibit an increased risk of falling.

Bisphenol A exposure is not associated with area-level socioeconomic index in Australian children using pooled urine samples

Bisphenol A (BPA) is used extensively in food-contact materials and has been detected routinely in populations worldwide, and this exposure has been linked to a range of negative health outcomes in humans. There is some evidence of an association between BPA and different socioeconomic variables which may be the result of different dietary patterns. The aim of this study was to conduct a preliminary investigation of the association between BPA and socioeconomic status in Australian children using pooled urine specimens and an area level socioeconomic index. Surplus pathology urine specimens collected from children aged 0-15 years in Queensland, Australia as samples of convenience (n = 469) were pooled by age, sex and area level socioeconomic index (n = 67 pools), and analysed for total BPA using online solid phase extraction LC-MS/MS. Concentration ranged from 1.08-27.4 ng/ml with geometric mean 2.57 ng/ml, and geometric mean exposure was estimated as 70.3 ng/kg d-1. Neither BPA concentration nor excretion was associated with age or sex, and the authors found no evidence of an association with socioeconomic status. These results suggest that BPA exposure is not associated with socioeconomic status in the Australian population due to relatively homogenous exposures in Australia, or that the socioeconomic gradient is relatively slight in Australia compared with other OECD countries.

The psychological and economic factors that influence energy consumption habits of low-income earners

Social marketers and governments have often targeted hard to reach or vulnerable groups (Gordon et al., 2006) such as young adults and low income earners. Past research has shown that low-income earners are often at risk of poor health outcomes and diminished lifestyle (Hampson et al., 2009; Scott et al., 2012). Young adults (aged 18 to 35) are in a transition phase of their life where lifestyle preferences are still being formed and are thus a useful target for long-term sustainable change. An area of focus for all levels of government is the use of energy with an aim to reduce consumption. There is little research to date that combines both of these groups and in particular in the context of household energy usage. Research into financially disadvantaged consumers is challenging the notion that that low income consumer purchasing and usage of products and services is based upon economic status (Sharma et al., 2012). Prior research shows higher income earners view items such as televisions and computers as necessities rather than non-essential (Karlsson et al., 2004). Consistent with this is growing evidence that low income earners purchase non-essential, energy intensive electronic appliances such as multiple big screen TV sets and additional refrigerators. With this in mind, there is a need for knowledge about how psychological and economic factors influence the energy consumption habits (e.g. appliances on standby power, leaving appliances turned on, running multiple devices at one time) of low income earners. Thus, our study sought to address the research question of: What are the factors that influence young adult low-income earners energy habits?

Introduction : studying Indonesian media worlds at the intersections of area and cultural studies

When preparing this special issue,1 our discussions with the editorial board of the International Journal of Cultural Studies (IJCS) included a moment of simultaneous surprise and reflection, which we would like to use as a starting point for our introduction to the articles appearing here. This occurred during communications about the number and length of the articles required for a special issue. The board’s representative stipulated that a specific number of articles were to be written by Indonesian scholars. The request surprised us. We had neither discussed nor anticipated ethnic or national quotas for authorial participation. But although the request caught us off guard it also stimulated us to think about the two disciplinary terrains traversed in the articles to follow.

Increasing leucine concentration stimulates mechanistic target of rapamycin signaling and cell growth in C2C12 skeletal muscle cells

Leucine is a key amino acid for initiating translation in muscle cells, but the dose-dependent effects of leucine on intracellular signaling are poorly characterized. This study examined the effect that increasing doses of leucine would have on changes in mechanistic target of rapamycin (mTOR)–mediated signaling, rates of protein synthesis, and cell size in C2C12 cells. We hypothesized that a leucine “threshold” exists, which represents the minimum stimulus required to initiate mTOR signaling in muscle cells. Acute exposure to 1.5, 3.2, 5.0, and 16.1 mM leucine increased phosphorylation of mTORSer2448 (~1.4-fold; P < .04), 4E-BP1 Thr37/46 (~1.9-fold; P < .001), and rpS6Ser235/6 (~2.3-fold; P < .001). However, only p70S6kThr389 exhibited a dose-dependent response to leucine with all treatments higher than control (~4-fold; P < .001) and at least 5 mM higher than the 1.5-mM concentration (1.2-fold; P < .02). Rates of protein synthesis were not altered by any treatment. Seven days of exposure to 0.5, 1.5, 5.0, and 16.5 mM leucine resulted in an increase in cell size in at least 5 mM treatments (~1.6-fold, P < .001 vs control). Our findings indicate that even at low leucine concentrations, phosphorylation of proteins regulating translation initiation signaling is enhanced. The phosphorylation of p70S6kThr389 follows a leucine dose-response relationship, although this was not reflected by the acute protein synthetic response. Nevertheless, under the conditions of the present study, it appears that leucine concentrations of at least 5 mM are necessary to enhance cell growth.

Sortase A : an ideal target for anti-virulence drug development

Sortase A is a membrane enzyme responsible for the anchoring of surface-exposed proteins to the cell wall envelope of Gram-positive bacteria. As a well-studied member of the sortase subfamily catalysing the cell wall anchoring of important virulence factors to the surface of staphylococci, enterococci and streptococci, sortase A plays a critical role in Gram-positive bacterial pathogenesis. It is thus considered a promising target for the development of new anti-infective drugs that aim to interfere with important Gram-positive virulence mechanisms, such as adhesion to host tissues, evasion of host defences, and biofilm formation. The additional properties of sortase A as an enzyme that is not required for Gram-positive bacterial growth or viability and is conveniently located on the cell membrane making it more accessible to inhibitor targeting, constitute additional reasons reinforcing the view that sortase A is an ideal target for anti-virulence drug development. Many inhibitors of sortase A have been identified to date using high-throughput or in silico screening of compound libraries (synthetic or natural), and while many have proved useful tools for probing the action model of the enzyme, several are also promising candidates for the development into potent inhibitors. This review is focused on the most promising sortase A inhibitor compounds that are currently in development as leads towards a new class of anti-infective drugs that are urgently needed to help combat the alarming increase in antimicrobial resistance.

Wide area control of SVCs for first swing stabilisation and damping in longitudinal systems

A non-linear Kalman filter based control strategy for SVCs located in major load groups is presented. This focusses on the limitation and damping of inter-area modes. It does this through treating local modes as noise and uses a tunable nonlinear control algorithm to improve both first swing stability and system damping. Simulation on a four machine system shows that the Kalman filer can successfully lock on to a desired inter-area mode and obtain a 31% improvement in critical clearing time as well as improved damping.

Orexin/hypocretin role in reward: implications for opioid and other addictions

Addiction is a devastating disorder that affects 15.3 million people worldwide. While prevalent, few effective treatments exist. Orexin receptors have been proposed as a potential target for anti-craving medications. Orexins, also known as hypocretins, are neuropeptides produced in neurons of the lateral and dorsomedial hypothalamus and perifornical area, which project widely throughout the brain. The absence of orexins in rodents and humans leads to narcolepsy. However, orexins also have an established role in reward seeking. This review will discuss some of the original studies describing the roles of the orexins in reward seeking as well as specific works that were presented at the 2013 International Narcotics Research Conference. Orexin signalling can promote drug-induced plasticity of glutamatergic synapses onto dopamine neurons of the ventral tegmental area (VTA), a brain region implicated in motivated behaviour. Additional evidence suggests that orexin signalling can also promote drug seeking by initiating an endocannabinoid-mediated synaptic depression of GABAergic inputs to the VTA, and thereby disinhibiting dopaminergic neurons. Orexin neurons co-express the inhibitory opioid peptide dynorphin. It has been proposed that orexin in the VTA may not mediate reward per se, but rather occludes the ‘anti-reward’ effects of dynorphin. Finally, orexin signalling in the prefrontal cortex and the central amygdala is implicated in reinstatement of reward seeking. This review will highlight recent work describing the role of orexin signalling in cellular processes underlying addiction-related behaviours and propose novel hypotheses for the mechanisms by which orexin signalling may impart drug seeking.

A deformable Brodmann area atlas

Functional MRI studies commonly refer to activation patterns as being localized in specific Brodmann areas, referring to Brodmann’s divisions of the human cortex based on cytoarchitectonic boundaries [3]. Typically, Brodmann areas that match regions in the group averaged functional maps are estimated by eye, leading to inaccurate parcellations and significant error. To avoid this limitation, we developed a method using high-dimensional nonlinear registration to project the Brodmann areas onto individual 3D co-registered structural and functional MRI datasets, using an elastic deformation vector field in the cortical parameter space. Based on a sulcal pattern matching approach [11], an N=27 scan single subject atlas (the Colin Holmes atlas [15]) with associated Brodmann areas labeled on its surface, was deformed to match 3D cortical surface models generated from individual subjects’ structural MRIs (sMRIs). The deformed Brodmann areas were used to quantify and localize functional MRI (fMRI) BOLD activation during the performance of the Tower of London task [7].