Daily Scheduled High Fat Meals Moderately Entrain Behavioral Anticipatory Activity, Body Temperature, and Hypothalamic c-Fos Activation

When fed in restricted amounts, rodents show robust activity in the hours preceding expected meal delivery. This process, termed food anticipatory activity (FAA), is independent of the light-entrained clock, the suprachiasmatic nucleus, yet beyond this basic observation there is little agreement on the neuronal underpinnings of FAA. One complication in studying FAA using a calorie restriction model is that much of the brain is activated in response to this strong hunger signal. Thus, daily timed access to palatable meals in the presence of continuous access to standard chow has been employed as a model to study FAA in rats. In order to exploit the extensive genetic resources available in the murine system we extended this model to mice, which will anticipate rodent high fat diet but not chocolate or other sweet daily meals (Hsu, Patton, Mistlberger, and Steele; 2010, PLoS ONE e12903). In this study we test additional fatty meals, including peanut butter and cheese, both of which induced modest FAA. Measurement of core body temperature revealed a moderate preprandial increase in temperature in mice fed high fat diet but entrainment due to handling complicated interpretation of these results. Finally, we examined activation patterns of neurons by immunostaining for the immediate early gene c-Fos and observed a modest amount of entrainment of gene expression in the hypothalamus of mice fed a daily fatty palatable meal

‘Stop Measuring Black Kids with a White Stick’: Translanguaging for Classroom Assessment

In this conceptual paper, we explore the opportunities and challenges that translanguaging may provide for students from Australian Aboriginal backgrounds and their teachers. We use examples taken from Australian Aboriginal students who may speak Standard Australian English, Australian Aboriginal English, creoles (Kriol being the common one across the north of Australia) and traditional languages (e.g. Kija, Martu). We begin by examining the concept of translanguaging and show how Australian Aboriginal students can move fluidly between their various linguistic resources, dialects and repertoires to make meaning, express their thoughts, understandings and feelings, create their identities, and do so in often playful and creative ways. The principles of fair and valid assessment are explored and the role that translanguaging can fulfil for assessment purposes is considered. We also document some of the social, cultural and linguistic biases that underpin aspects of assessment, and make suggestions for improvement. In particular, we examine how teachers could approach assessment so that students with Aboriginal backgrounds are able to draw on their full linguistic repertoire and, in this way, address the issues surrounding discriminatory assessment practices that are founded on monolingual mindsets. We also take up the gauntlet to ‘stop measuring black kids with a white stick’ and seek positive and embracing ways for all students with Aboriginal backgrounds to engage in assessment practices

An electrophysiological assessment of the use of stem cells in neurological disease modelling and therapy

Electrophysiology is the best discipline to functionally characterise neuronal behaviour, as such, electrophysiology plays a key role in neurological disease modelling and therapy. Totipotent stem cells have the limitless possibility to differentiate into any type of cell within the human body and therefore used frequently in disease modelling and therapy. This thesis aims to electrophysiologically assess the use of stem cells in disease modelling and therapy across two diseases; the infantile epilepsy disorder - cyclin dependant kinase like 5 (CDKL5) deficiency, and the fatal neurodegenerative condition - Huntington’s Disease, respectively. This thesis shows that a patient induced pluripotent stem cell derived cortical neuronal model of CDKL5-deficiency recreates the epilepsy seen in patients, providing a valid disease model. Furthermore, these neurons can be cultured on a high-throughput multi-electrode array for the rapid testing of novel therapeutic compounds. In the disease therapy side of the project, stem cell grafts fail to functionally integrate synaptically into a rat model of Huntington’s Disease (HD), however restore synaptic function in the lesioned striatum. These data suggest that the stem cell graft may provide therapeutic benefits, just not electrophysiologically. Taken together, these observations suggest that stem cells can reproduce the defining clincal charactersistics, epilepsy, lacking from other model systems in an infantile epilepsy model and induce acute therapeutic benefits in a rodent model of HD

Heat shock factor 1 regulates lifespan as distinct from disease onset in prion disease

Prion diseases are fatal, transmissible, neurodegenerative diseases caused by the misfolding of the prion protein (PrP). At present, the molecular pathways underlying prion-mediated neurotoxicity are largely unknown. We hypothesized that the transcriptional regulator of the stress response, heat shock factor 1 (HSF1), would play an important role in prion disease. Uninoculated HSF1 knockout (KO) mice used in our study do not show signs of neurodegeneration as assessed by survival, motor performance, or histopathology. When inoculated with Rocky Mountain Laboratory (RML) prions HSF1 KO mice had a dramatically shortened lifespan, succumbing to disease ≈20% faster than controls. Surprisingly, both the onset of home-cage behavioral symptoms and pathological alterations occurred at a similar time in HSF1 KO and control mice. The accumulation of proteinase K (PK)-resistant PrP also occurred with similar kinetics and prion infectivity accrued at an equal or slower rate. Thus, HSF1 provides an important protective function that is specifically manifest after the onset of behavioral symptoms of prion disease

Intention, beliefs and mood assessed using electronic diaries predicts attendance at cardiac rehabilitation:An observational study

Background: Cardiac rehabilitation is effective in promoting physical/psychological recovery following acute coronary syndrome. Yet, rates of attendance at outpatient cardiac rehabilitation by eligible patients are low. Objectives: This study examined the determinants of attendance at outpatient cardiac rehabilitation in acute coronary syndrome patients following discharge until cardiac rehabilitation commencement. Design: A weekly electronic diary measured cardiac-related cognitions and mood and examined their relation to attendance at outpatient cardiac rehabilitation. Settings: Three United Kingdom National Health Service secondary care settings in two Health Board areas in Scotland. Participants: Acute coronary syndrome patients were recruited from March 2012 to June 2013 prior to hospital discharge. Of 488 eligible patients referred for cardiac rehabilitation, 214 consented. Results: 166 participants provided, on average, 5 weeks of diary entries before cardiac rehabilitation commenced. High intention (i.e. low “do not intend”) to attend CR and its rate of increase over time predicted attendance. Low negative emotional representation, high perceived necessity, high confidence in maintaining function, low negative affect, and high positive affect following discharge predicted attendance at cardiac rehabilitation. The rate of change in cardiac-related mood and these cognitions was not predictive. Baseline and rate of change in “do not intend” entirely mediated relationships between a) perceived necessity, b) negative affect and attendance at cardiac rehabilitation. Conclusions: Negative affect in the first weeks following discharge represents the key challenge to a patient maintaining their intention to attend cardiac rehabilitation. Intervention to improve attendance should focus on improving intention to attend following discharge and during recovery by improving patient understanding of cardiac rehabilitation and reducing negative affect

Measles virus causes immunogenic cell death in human melanoma

Oncolytic viruses (OV) are promising treatments for cancer, with several currently undergoing testing in randomised clinical trials. Measles virus (MV) has not yet been tested in models of human melanoma. This study demonstrates the efficacy of MV against human melanoma. It is increasingly recognised that an essential component of therapy with OV is the recruitment of host anti-tumour immune responses, both innate and adaptive. MV-mediated melanoma cell death is an inflammatory process, causing the release of inflammatory cytokines including type-1 interferons and the potent danger signal HMGB1. Here, using human in vitro models, we demonstrate that MV enhances innate antitumour activity, and that MV-mediated melanoma cell death is capable of stimulating a melanoma-specific adaptive immune response