The Role of the DIRAS Family Members in Regulating Ras Function, Cancer Growth and Autophagy

DIRAS3 is a maternally imprinted tumor suppressor gene that is downregulated by multiple mechanisms across several tumor types. When re-expressed, DIRAS3 decreases proliferation, inhibits motility, and induces autophagy and tumor dormancy. DIRAS3 encodes a 26 kDa small GTPase with 60% homology to Ras and Rap, differing from oncogenic Ras family members by a 34-amino acid N-terminal extension that is required for its tumor suppressive function in ovarian cancer. By assessing the structure-function relationship, I found that DIRAS3 inhibits Ras-induced transformation and is a natural antagonist of Ras/MAPK signaling. DIRAS3 binds directly to Ras and disrupts cluster formation inhibiting the activation of Raf kinase, which is dependent upon membrane localization and the N-terminal extension. This observation provides a novel approach to target oncogenic Ras and assesses the functional significance of Ras clustering/multimerization. The N-terminus of DIRAS3 also plays an important role in the mechanism(s) by which DIRAS3 induces autophagy. Expression of DIRAS3 is required for the induction of autophagy in human cells. While DIRAS3 is found in the genome of humans, pigs and cows, it maps to an apparent evolutionary breakpoint in the rodent lineage where chromosomes have been rearranged relative to the human genome since the two species shared a common ancestor. Mice and humans do express two homologous Ras-related GTPases, DIRAS1 and DIRAS2. These 22-kDa GTPases have 30-40% homology with H-Ras and 50-60% homology with DIRAS3 where the major difference is the truncation of the N-terminal extension. DIRAS1 and DIRAS2 have not previously been studied extensively. I compared the roles of the DIRAS family in malignant transformation, proliferation, survival, motility and autophagy. My observations document the role of DIRAS1 and DIRAS2 as ovarian cancer tumor suppressors and demonstrate their role in autophagy and autophagic cell death. Similar to DIRAS3, DIRAS1 and DIRAS2 induce autophagy at several different levels, including transcription-dependent mechanisms. DIRAS1 and DIRAS2 likely serve as surrogates for DIRAS3 in the murine genome, playing an essential role in murine autophagy. These studies are fundamentally important as they explore the functional significance of their N-terminal extensions, helping to explain how members of an oncogenic superfamily acquire tumor suppressor function

A Colourful Approach To Reducing Examination Anxiety

This paper examines the use of visual aids in examinations and provides interesting and innovative ideas for educators in higher education institutions. It shows a clear link between the use of colour and technology and the reduction of examination anxiety. Traditionally examinations tended to be in written format only, questions were multiple choice, short answer, essay or case study based. This paper showcases an innovative approach to examinations where videos and photos are use to supplement traditional methods. A sound theoretical foundation is provided to support the use of the innovative methods utilized. The paper not only provides information for educators on how to approach this idea but more importantly documents student feedback on the successful implementation of the concept

Putting Bling In The Classroom

This paper showcases the innovative use of a case study in action.  It initially introduces a case study on the bottled water ‘bling’ and its phenomenal success in recent times.  From a marketing educator’s point of view it provides an example of how to bring reality to the class room and gives students hands on consumer experience through active learning.  Details are provided on the in-class activity consisting of the case study, questions and guidelines for conducting the practice-orientated exercise.  The paper concludes with student feedback on the activity, which highlights the level of student engagement and motivation to learning and class participation.  It clearly shows that immersing students in the experience through active learning improves learning outcomes through concretisation of the concepts discussed in class. It also provides educators with recommendations for replicating this exercise

Innovating Through Structured Curriculum Development

Structured and innovative curriculum development can have a profound impact on learning outcomes.  This paper provides interesting and innovative ideas for educators in higher education institutions to allow them to achieve improved learning outcomes.  This paper showcases how engaging students throughout the course and supporting them through consistent, incremental course development leads to innovative curriculum development.  The improved course structure and students’ increased engagement achieve maximum learning outcomes.  Various research studies support the use of innovative methods though not much is said about consistency of assessments and course structure in curriculum development with the aim to reduce exam anxiety and ultimately enhance learning outcomes.  In our unit of study, seminar presentations and poster sessions in conference style were used to engage students and introduce them to a different way of learning other than reports.  The paper not only provides information for educators on how to design engaging course structures but more significantly supports the outcomes through the analysis of student feedback based on objective teaching evaluation conducted before exams

Enhancing Learning Outcomes Through Application Driven Activities In Marketing

This paper introduces an activity used in class to allow students to apply previously acquired information to a hands-on task. As the authors have previously shown active learning is a way to effectively facilitate and improve students’ learning outcomes. As a result to improve learning outcomes we have overtime developed a series of learning activities reinforcing marketing theories. In this paper, we provide details of a marketing communications exercise which in addition to being a vehicle for active learning also allowed students to apply the results of their previous research thereby effectively aligning all learning and assessment tasks. The activity required students to take a previously completed environmental analysis of a foreign country and using that information develop a print advertisement for an Australian branded product unavailable in that country. Details are provided on the in-class activity including guidelines for conducting the practice-orientated exercise and information on the assessment tasks leading up to this activity. The paper provides academics with an example of how to apply concepts to real life examples in the classroom and give students hands on experience and further shows how learning can be scaffolded through assessment. We found that students actively engaged in the experience and improved their learning outcomes through application of their previous research and the concepts discussed in class

Individual Differences in Cognitive Map Accuracy: Investigating the Role of Landmark Familiarity

Broad individual differences exist in the ability to create a cognitive map of a new environment. The current studies investigated whether familiarizing participants with to-be-learned target landmarks (Experiment 1) or target landmarks plus the order they would be encountered along routes (Experiment 2) before exploring the Silcton virtual environment would increase performance on tasks assaying spatial memory of Silcton. Participants in both experiments were randomly assigned to be pre-exposed either to information about target landmarks in Silcton or control landmarks on the university campus. In both experiments, participants explored Silcton via four prescribed routes and then performed a direction estimation task and a map building task based on memory for the locations of the target landmarks. In addition, participants completed the Spatial Orientation Test of perspective-taking. Pre-exposure to Silcton landmarks versus control landmarks did not affect scores on Silcton-based tasks in either experiment. Some sex differences in direction estimation were observed in Experiment 1 but not Experiment 2. While facilitating familiarity with landmarks did not improve cognitive map accuracy, both sex and perspective taking ability were found to contribute to individual differences in the ability to create a cognitive map

Sex Differences and Cognitive Maps: Studies in the Lab don’t Always Reflect Cognitive Map Accuracy in Everyday Life

The ability to create an accurate mental survey representation, or cognitive map, when moving through an environment varies widely across individuals, and we are still trying to understand the origins of these individual differences. Non-immersive virtual environments used to test for cognitive map accuracy in the laboratory have shown sex differences with a performance advantage for men in some studies but not others. When sex differences are demonstrated, it is unclear whether women’s performance generalizes to familiar and unfamiliar real-world environments. In Experiment 1, 98 participants explored the virtual environment Silcton and afterwards estimated directions between the landmarks in Silcton and arranged landmarks found in Silcton on a map. In addition, they reported frequently visited real-world locations and then estimated directions between them and drew a map of the locations. Men were more accurate on tests of Silcton than women were, although there was no difference between sexes for accuracy with real-world locations. Within sexes, women were more accurate with the real-world locations than Silcton, while men showed the opposite pattern. In Experiment 2, 21 women were tested with Silcton and their familiar real-world locations as in Experiment 1 but were also walked through an unfamiliar real-world area on campus and completed direction estimation and map drawing tests for the new environment. Overall, women were more accurate with the two real-world environments than Silcton, with some evidence that accuracy with the new real-world environment was more accurate than the familiar real-world locations. Overall, women’s ability to create a cognitive map of a virtual environment in the laboratory does not seem to be indicative of their ability to do the same in the real world, and care should be taken when generalizing lab results with virtual environments