The Role of MED12, Notch1, and Notch3 in Adipose Stem Cell Self-Renewal and The Integrated Use of Stem Cells in Public Educational Materials

Human adipose-derived mesenchymal stem cells offer significant therapeutic potential as an ethically sound, easily accessed source of adult stem cells. To harness their medically relevant properties, it is necessary to understand the mechanisms that control their fate. Cell state and differentiation of stem cells is determined by interactions of signaling pathways, chromatin modifiers, and transcription factors working to regulate cell-type specific gene expression profiles. Specifically, both the MED12 subunit of the Mediator complex and the Notch signaling pathway are known to individually influence hASC self-renewal. We investigated the relationship between Notch signaling and transcriptional cofactor, MED12, to elucidate a potential regulatory relationship and better understand the mechanisms that determine cell fate in hASCs. Using siRNA mediated knockdowns, we analyzed the expression and activation changes of Notch signaling in self-renewing adipose stem cells in the presence of reduced MED12. Knockdown validation, Notch expression and signaling pathway activation was quantitated via qRT-PCR and western blot analysis. Subsequently, we observed that MED12 is required for the activation of the Notch3 signaling pathway, while Notch1 signaling is not significantly influenced by the reduction of MED12, suggesting a novel regulatory interface between MED12 and the Notch3 signaling pathway. Understanding the relationship between MED12, Notch1, and Notch3 and their influence on self-renewal will increase understanding of hASC cell fate mechanisms, indicating a need for further investigation, and aiding in better determining their potential for applications in regenerative medicine. Furthermore, to advance support for scientific investigation and essential stem cell research, public education of the basic science and medical relevance of stem cells must also be addressed. An interactive children’s book was developed to integrate basic science research and stem cell concepts inside and out of formal educational facilities. Specifically designed as an educational book for students, a tool for educators, and a resource for the community, this book aims to effectively communicate fact-based stem cell content, address misconceptions, and promote positive engagement and interest in the sciences. This thesis provides evidence of a novel regulatory relationship between Notch signaling and MED12 and contributes, via educational resource, to advancing support for essential stem cell research. Collectively, this aids in the elucidating the potential use and benefits of adipose stem cells in clinical therapeutics and regenerative medicine

Investigating the Role of MED12, Notch1, and Notch3 Interactions in the Self-Renewal and Adipogenesis of hASCs and their Integrated use in Public Educational Materials

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Calls to a home birth helpline: empowerment in childbirth

In the UK a woman has the right to decide to give birth at home, irrespective of whether she is expecting her first or a subsequent child and of any perceived ‘risk’ factors. However, the rate of home births in the UK is very low (around 2%), varies widely across the country and many women do not know how to arrange midwifery cover. The Home Birth helpline is a UK-based voluntary organisation offering support and information for women planning a home birth. In order to gain direct access to the issues that are of concern to women when planning a home birth, 80 calls to the helpline were recorded. The aims of this paper are to document the problems that callers to this helpline report having when trying to arrange home births and to explore the strategies the call-taker uses in helping women to exercise their right to birth at home. The paper concludes that women are not easily able to exercise their right to choose the place of birth and suggests a number of recommendations for action

Risk of Aneurysm Rupture (ROAR) study: protocol for a long-term, longitudinal, UK multicentre study of unruptured intracranial aneurysms

Introduction Unruptured intracranial aneurysms (UIA) are common in the adult population, but only a relatively small proportion will rupture. It is therefore essential to have accurate estimates of rupture risk to target treatment towards those who stand to benefit and avoid exposing patients to the risks of unnecessary treatment. The best available UIA natural history data are the PHASES study. However, this has never been validated and given the known heterogeneity in the populations, methods and biases of the constituent studies, there is a need to do so. There are also many potential predictors not considered in PHASES that require evaluation, and the estimated rupture risk is largely based on short-term follow-up (mostly 1 year). The aims of this study are to: (1) test the accuracy of PHASES in a UK population, (2) evaluate additional predictors of rupture and (3) assess long-term UIA rupture rates.Methods and analysis The Risk of Aneurysm Rupture study is a longitudinal multicentre study that will identify patients with known UIA seen in neurosurgery units. Patients will have baseline demographics and aneurysm characteristics collected by their neurosurgery unit and then a single aggregated national cohort will be linked to databases of hospital admissions and deaths to identify all patients who may have subsequently suffered a subarachnoid haemorrhage. All matched admissions and deaths will be checked against medical records to confirm the diagnosis of aneurysmal subarachnoid haemorrhage. The target sample size is 20 000 patients. The primary outcome will be aneurysm rupture resulting in hospital admission or death. Cox regression models will be built to test each of the study’s aims.Ethics and dissemination Ethical approval has been given by South Central Hampshire A Research Ethics Committee (21SC0064) and Confidentiality Advisory Group support (21CAG0033) provided under Section 251 of the NHS Act 2006. The results will be disseminated in peer-reviewed journals.Trial registration number ISRCTN17658526