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The importance of miRNAs in regulating gene expression has been addressed in several haematological cancers including myelodysplastic syndrome (MDS). In MDS, miR-145 and miR-146a have been associated with some of phenotypic features of 5q- syndrome. Monosomy 7/7q deletion is the second most common chromosomal abnormality in MDS and identifies a subgroup of patients with poor prognosis. Thus far, no studies have examined the role of miRNA dysregulation in MDS patients with monosomy 7. In this study we examined the functional consequences of deletion of miRNAs localized to 7q with particular focus on miR-595, which is localized to 7q36.3, which is commonly deleted region in 7q- and -7. Most of the available methodologies for miRNA target identification are based on computational algorithms. Therefore, there is a relatively high incidence of false positive target identification. To enable the identification of biologically relevant microRNA targets, a novel functional assay was developed in our lab, which is based on positive/negative selection (Gaken et al, 2012). Using this assay, I identified functional targets of miR-595 and correlated this with the MDS phenotype. Applying the functional assay to identify targets for miR-595 resulted in the identification of several targets including RPL27A, a large ribosomal subunit protein that was validated as a target for miR-595 by qRT-PCR and western blot analysis. Given the recognised association of ribosomal protein (RPS14) with 5q- syndrome, subtype of MDS, I assessed the biological function of RPL27A in order to identify its contribution to the disease pathogenesis. Using Polysomes fractionation,. RPL27A knockdown showed a reduction in the large ribosomal subunit (60S). On day 6 of the knockdown, the depletion of RPL27A led to p53 activation and induced variable levels of apoptosis in all cell lines. Interestingly, like RPS14 knockdown, the effect of RPL27A knockdown in 48 h was p53 dependent. The p53 independent effect, which was observed on day 6, was attributed to a defect in ribosome biogenesis based on the disruption of nucleolar staining in HCT-116 and HCT-116 p53-/- with depleted RPL27A using fibrillarin antibody and similar effects were seen with RPS14.

This study opens with an introduction to the transpersonal orientation, which Boucouvalas presents as a meta-framework of the transpersonal field that includes individual, group/societal, and planetary/cosmic domains. Three major theoretical perspectives of the field framed the study: the hierarchical stages of development, spiral path, and participatory. I offer a philosophical hermeneutic reading of the Qur'an to trace the development of human collective consciousness as a construct of the interaction between the autonomous and homonomous self at the individual, group, and cosmic levels on one plane of reality with the Divine on the other. This analysis, which utilizes Gadamer's conceptualization of philosophical hermeneutics as a research philosophy, concludes that this process of collective human development is comprised of three clearly distinct representations: familial, national, and cosmic/planetary. I articulate development and growth as a process of the expansion of collective consciousness. The cosmic/planetary human consciousness represents the ultimate reach of this expansion, for it assimilates the national and familial types while simultaneously transforming and transcending them within its reach. Based on the historical development of human consciousness in the Qur'an depicted in this study, I propose that human collective consciousness has reached the domains of cosmic consciousness, which began at the time of the Qur'an being read by Muhammad. However, individuals and groups may still operate within the limiting boundaries of national consciousness in the form of religious, ethnic, racial, and nation states. The Qur'an, and possibly other religious texts, should be understood within this expanded cosmic/planetary consciousness reach because they represent humanity's collective heritage. Moreover, those individuals operating within a strictly national consciousness should not be entrusted with explaining these texts to humanity at large or imposing their own limiting understanding on the world. I conclude by outlining some implications for adult education as a process, a program and a movement. I presented the possible contribution of a transpersonal adult learning theory based on this study's meta-framework as a comprehensive worldview to adult education and learning combining multiple dimensions of being, including the rational, affective, spiritual, imaginative, somatic, and sociocultural domains through relevant experiences of body-mind-spirit.