Targeting amino acid transport in metastatic castration-resistant prostate cancer : effects on cell cycle, cell growth, and tumor development

Background L-type amino acid transporters (LATs) uptake neutral amino acids including L-leucine into cells, stimulating mammalian target of rapamycin complex 1 signaling and protein synthesis. LAT1 and LAT3 are overexpressed at different stages of prostate cancer, and they are responsible for increasing nutrients and stimulating cell growth. Methods We examined LAT3 protein expression in human prostate cancer tissue microarrays. LAT function was inhibited using a leucine analog (BCH) in androgen-dependent and -independent environments, with gene expression analyzed by microarray. A PC-3 xenograft mouse model was used to study the effects of inhibiting LAT1 and LAT3 expression. Results were analyzed with the Mann-Whitney U or Fisher exact tests. All statistical tests were two-sided. Results LAT3 protein was expressed at all stages of prostate cancer, with a statistically significant decrease in expression after 4–7 months of neoadjuvant hormone therapy (4–7 month mean = 1.571; 95% confidence interval = 1.155 to 1.987 vs 0 month = 2.098; 95% confidence interval = 1.962 to 2.235; P = .0187). Inhibition of LAT function led to activating transcription factor 4–mediated upregulation of amino acid transporters including ASCT1, ASCT2, and 4F2hc, all of which were also regulated via the androgen receptor. LAT inhibition suppressed M-phase cell cycle genes regulated by E2F family transcription factors including critical castration-resistant prostate cancer regulatory genes UBE2C, CDC20, and CDK1. In silico analysis of BCH-downregulated genes showed that 90.9% are statistically significantly upregulated in metastatic castration-resistant prostate cancer. Finally, LAT1 or LAT3 knockdown in xenografts inhibited tumor growth, cell cycle progression, and spontaneous metastasis in vivo. Conclusion Inhibition of LAT transporters may provide a novel therapeutic target in metastatic castration-resistant prostate cancer, via suppression of mammalian target of rapamycin complex 1 activity and M-phase cell cycle genes.

An ICT Implementation Strategy for Primary Schools in Fiji

Information and Communication Technology (ICT) has been embraced with hope and optimism in both developing and developed countries. While in the developed countries most citizens have access to one or many of the devices which utilize this technology (e.g. desktop, laptop, tablet, mobile phone), in developing countries this “luxury” can only be afforded by a privileged few. The use of these technologies in primary schools in developing countries is low. This is due to the fact that there are other bigger issues that some of these countries have to grapple with such as meeting the basic health and education needs of its citizens. Quality primary education and global development partnerships are two of the eight Millennium Development Goals of the United Nations (UNDP, 2012). Many Governments, NGO’s, service organizations, and individuals in developing countries are always looking at ways in which the disparity (not just in terms of ICT) can be narrowed. There has to be a greater collaboration between stakeholders in developing and developed countries (Mutonyi & Norton, 2007). How do stakeholders from developed countries engage with partners in developing countries to deliver meaningful and relevant outcomes for primary school students using ICT? As a first step getting the key stakeholders on side is critical. In the Fijian context, schools are managed and run by committees who are members of the community. Therefore, getting the committee on side together with the head-teachers and teachers is critical. Conversations about teaching and learning with technology can then follow with greater ease. The sustainability of any innovative approaches is also an essential element of this equation. Through this lens, this chapter investigates how ICT can be implemented in primary schools in Fiji. It proposes a three-layered approach which focuses on: (1) the community, school leadership, and teachers; (2) content, pedagogy, and technology, and (3) sustainability.

The burning season

"Every year deliberately lit fires rage across Indonesia. They destroy pristine rainforest, endanger orangutans and contribute to climate change. A young carbon trading entrepreneur goes in search of a solution." "Dorjee Sun, a young Australian Entrepreneur, believes there's money to be made from protecting rainforests in Indonesia, saving the orangutan from extinction and making a real impact on climate change. Armed with a laptop and a backpack, he sets out across the globe to find investors in his carbon trading scheme. It is a battle against time. Achmadi, the palm oil farmer is ready to set fire to his land to plant more palm oil, and Lone's orangutan centre has reached crisis point with over 600 orangutans rescued from the fires. The Burning Season is an eco-thriller about a young man not afraid to confront the biggest challenge of our time."

Australian consumer attitudes and decision making on renewable energy technology and its impact on the transformation of the energy sector

This paper critically examines research on consumer attitudes and behavior towards solar photovoltaic (PV) and renewable energy technology in Australia. The uptake of renewable energy technology by residential consumers in Australia in the past decade has transformed the electricity supply and demand paradigm. Thus, this paper reviews Australian research on consumer behavior, understanding and choices in order to identify gaps in knowledge. As the role of the consumer transforms there is a critical need to understand the ways consumers may respond to future energy policies to mitigate unforeseen negative social and economic consequence of programs designed to achieve positive environmental outcomes.

Potentiation of the early visual response to learned danger signals in adults and adolescents

The reinforcing effects of aversive outcomes on avoidance behaviour are well established. However, their influence on perceptual processes is less well explored, especially during the transition from adolescence to adulthood. Using electroencephalography, we examined whether learning to actively or passively avoid harm can modulate early visual responses in adolescents and adults. The task included two avoidance conditions, active and passive, where two different warning stimuli predicted the imminent, but avoidable, presentation of an aversive tone. To avoid the aversive outcome, participants had to learn to emit an action (active avoidance) for one of the warning stimuli and omit an action for the other (passive avoidance). Both adults and adolescents performed the task with a high degree of accuracy. For both adolescents and adults, increased N170 event-related potential amplitudes were found for both the active and the passive warning stimuli compared with control conditions. Moreover, the potentiation of the N170 to the warning stimuli was stable and long lasting. Developmental differences were also observed; adolescents showed greater potentiation of the N170 component to danger signals. These findings demonstrate, for the first time, that learned danger signals in an instrumental avoidance task can influence early visual sensory processes in both adults and adolescents.