GC-selective DNA-binding antibiotic, Mithramycin A, reveals multiple points of control in the regulation of Hdm2 protein synthesis

The primary role of the Hdm2/Mdm2 oncoprotein is to regulate the levels and activity of the transcription factor p53. Hdm2 synthesis is itself tightly controlled and, as demonstrated by a recently described SNP (SNP309) in the hdm2-P2 promoter, minor variations in Hdm2 expression have phenotypic consequences on radiation sensitivity and cancer predisposition. To further define mechanisms regulating Hdm2 expression, we have investigated the effects of the GC-selective DNA-binding drug, Mithramycin A (MA) on hdm2 mRNA transcription, trafficking, and translation. Firstly we show that the constitutive hdm2-P1 promoter is inhibited by MA. We define, for the first time, the minimal sequence elements that are required for P1-promoter activity and identify those which confer MA sensitivity. Secondly, MA induces p53-dependent transcription from the hdm2-P2 promoter. Thirdly, and critically, MA also inhibits Hdm2 synthesis at the post-transcriptional level, with negative effects on hdm2 mRNA nuclear export and translation. This study highlights the complex interplay between the pathways that regulate Hdm2 protein synthesis in cancer cells, and furthermore emphasizes the export of hdm2 mRNA from the nucleus to the cytoplasm as a key point of control in this process.<br/><br/

‘What Would Jesus Do?’: Toward a Grounded Theory of Born-Again Christians’ Process of Sanctification and Therapeutic Implications

Background: Integrating religious perspectives into psychological therapies is increasingly recommended by regulatory bodies (NICE, BPS, APA). However, there are no core competencies for clinicians working with a religious population such that for many therapists, faith (religious or spiritual), is treated as one aggregate psychological domain, if at all. This lack of nuance results in spiritually avoidant care, misaligned treatment goals between therapist and client, and poor therapeutic outcomes. Nowhere more so than with Christian clients who, due to the recent and rapid growth of ‘born-again’ Independent Protestantism, have largely evaded psychological inquiry. To address these shortcomings, a nuanced understanding of their self-concept and therapeutic implications are investigated. Methods: A Glaserian Grounded Theory on nine participants was performed. Results: The dominant reason born-again clients have poor agreement with therapeutic treatment is that their theory of sanctification conflicts with psychological theories of transformation. Their true-self, created by God, is discoverable only in relationship to Jesus and becoming like him through self-awareness, self-acceptance and self-surrender. This sanctification process constitutes Christ-actualisation, with implications for psychotherapy centring around how their true-self is understood. This include Christians’ distrust of emotions, specific types of cognitive restructuring, and spiritual aetiology of distress and fears around opening-up to any authority other than Jesus. Conclusions: A redefinition of being ‘Christian’ is needed as being in relationship. The nature of this relationship can be ascertained in assessment, formulation and treatment plan. Several models are provided to help the Psychologist decide upon an appropriate therapeutic modality, to aid formulation and frame a nuanced engagement with emotions and cognitions, and to help ascertain treatment goals in alignments with sanctification

The Role Of Octopamine In Syllable-Period Selective Phonotaxis In Female Cricket Acheta Domesticus

Female crickets respond phonotactically to the calls of conspecific males. Females\u27 phonotaxis has been reported to be variable, ranging from unselective to selectve in response to calls with varying syllable periods (30-90 ms). Octopamine, an intertebrate neurotransmitter, has been reported to increase aggressive behavior in crickets, (Stevanson et al. 2005) but the effects of octopamine on behaviors such as phonotaxis have not been investigated. The goal of this study is to determine the effects of octopamine on the syllable-period selective phonotactic response of females. Results suggest a decrease in phonotactic responsiveness shown by 5-10 day-okds after prothroacic nanoinjection of octopamine

Ritual as erotic anagogy in Pseudo-Dionysius: a Reformed critique

Martin Luther famously denounced Pseudo-Dionysius as ‘downright dangerous; he Platonizes more than he Christianizes.’ In this 500th year of the Reformation I critically examine Luther’s judgement firstly by exploring the Neoplatonic background to ritual in Dionysius, secondly by presenting a Reformed critique of this background and finally by arguing for a distinctively Christian Dionysius who survives this critique

Effectiveness Of An Aquatic Exercise Program For Reducing Weight, Body Fat And Chronic Low Back And Joint Pain

According to the World Health Organization (WHO), obesity has risen at an alarming rate and has reached epidemic proportions throughout the world (WHO, 2017). In the U. S., approximately 93.3 million U.S. adults are obese with an overall prevalence of 39.8 %. Chronic pain is another public health issue in the U.S, affecting almost 100 million people and is associated with significant annual healthcare costs and lost productivity (National Center for Complementary and Integrative Health [NCCIH], 2017). Exercise is considered one of the most effective prevention strategies for reducing obesity and has been documented to decrease chronic pain. The purpose of this Doctor of Nursing Practice (DNP) project was to determine if the WATERinMOTION aquatics exercise program was effective in promoting weight loss, decreasing percent body fat, and reducing chronic low back or joint pain. These aquatic programs were offered at two rural Young Men’s Christian Association (YMCA) sites. A pre/post-test, quasi-experimental design with a convenience sample (N = 11) was utilized. Participants completed a four or five-week aquatics exercise class which met twice a week. Pre/post-anthropometric measures (weight, percent body fat, and body mass index) and pre/post self-reported pain measurements were obtained using the numerical pain scale and survey questions about pain medication use. Upon analysis, statistically significant differences were observed in body weight (p = .005) and body mass index (p = .003) between the pre and post measurements. However, no significant differences were found in percent body fat (p = .113) or pain (p = .112). Despite, the classes being offered only twice a week for four or five weeks and use of a small sample size, participants in the WATERinMOTION aquatics exercise program did demonstrate some positive weight loss benefits

P-13 The Role of Octopamine in Selective Phonotaxis by Female Cricket Acheta Domesticus

Female crickets respond phonotactically to the calls of conspecific males. Females’ response has been reported to be variable, ranging from unselective to selective of calls with varying syllable periods (30–90 ms). Octopamine, an invertebrate neurotransmitter, has been reported to increase aggressive behavior in crickets (Stevenson et al. 2005), but the effects of octopamine on behaviors such as phonotaxis have not been investigated. The goal of this study is to determine the effects of octopamine on the syllable-period selective phonotactic response of females. Preliminary data suggests a decrease in phonotactic responsiveness shown by 5-10 day-olds after prothoracic nanoinjection of octopamine

Distributed Cognition as a framework for accessible design

In order to navigate the world, humans have historically made tools that allowed them to exploit their environment in ways beyond their natural physical and mental capacities. This continues to be true in the information age. Being able to use digital tools in this age affords the individual agency to influence and participate in the world and so it is critical that this capacity is equally available to all people. Current standards of accessibility attempt to create accommodations for overlooked populations in the form of guidelines, but these rely on a flawed approach to accessibility that is surface-level and lacks understanding of the populations to which it caters. However, distributed cognition offers an approach through which we can understand users through their interaction strategies with technology and through which we can understand technology as an extension of the mind. This paper explores the short-comings of current approaches to accessible design, how distributed cognition has been used to describe human-computer interactions and how this can be extended to understand accessible design. A case study of how a distributed cognition approach may transform accessible design for individuals with Autism Spectrum Condition is developed and discussed