A Novel Method to Analyze DNA Breaks and Repair in Human Cells

Microsatellites repeat sequences are prone to forming non-canonical DNA structures and mutations. These areas of the genome can undergo expansions and contractions and are responsible for a variety of inherited neurological and neuromuscular disorders. Hairpin structures formed by trinucleotide repeats can lead to replication fork stalling, and fork collapse causing DNA double strand breaks. Various mechanisms are involved in processing microsatellites including mismatch repair, base excision repair, and crossover junction endonuclease cleavage. These processes, which are supposed to protect the genome, could also be the culprits which are causing mutations. In order to test and study this hypothesis, the use of a two color marker gene assay to detect DNA double strand breaks at trinucleotide repeats, was used to detect replication fork stalling, and collapse in presence or absence of replication stress. An important mechanism for the restart of a stalled replication fork involves crossover junction endonucleases, which cleave obstacles that prevent passage of the replication fork. This process is led by MUS81 and its associates EME1 and EME2, which form complexes to process these secondary structures allowing the replication fork to progress. My results indicate distinct roles for MUS81-EME1 and MUS81-EME2 complexes in the maintenance of genome stability

Metaphors for Change: the Narrative Power of Domestic Space in Nineteenth and Twentieth Century British Women’s Writing

Domestic spaces carry layers of meaning. They evidence structural changes over time, representing different social and economic ideologies and priorities. Their spatial organisation affects the way that life is conducted within them. They are the physical sites of the complex elements that combine to create ‘home’. This thesis draws on theories of architecture, space, place, culture and society to explain how domestic settings reflect the psychological position of women protagonists who, for one reason or another, experience a personal imperative for change. It explores the notion of ‘home’, how living spaces and their contents are intimately connected with the experiences of the women who inhabit them and provide metaphors that illuminate moments of personal, social, political or economic change. The novels selected for study were written by women authors between the mid-nineteenth to late twentieth centuries, providing a time frame that encompasses major social changes including the Industrial Revolution, two World Wars and first- and second-wave feminist movements. The effect of such events on the positions and aspirations of individual women are reflected in the narratives of the selected novels. The thesis is structured in chapters that categorise the novels according to the conditions under which habitation occurs. This structure also provides a chronology, starting with the ordered spaces of the country house in the mid-nineteenth-century, moving on to consider borrowed spaces in rented accommodation in the interbellum and post-World War Two, serviced spaces accommodating paying guests between the 1930s and the 1970s, and finally the shared spaces of hostels, bedsits, families and communes between 1960 and 1985. The novels discussed in this thesis tell the stories of women who are considered transgressive because they try to break away from conventional living patterns. The domestic spaces they occupy carry meanings that reflect a state of being at a point of uncertainty or change

Laboratory Precipitation and Geochemical Investigation of Unstable CaCO\u3csub\u3e3\u3c/sub\u3e Polymorphs: Implications for the Origin of Precambrian “Molar-tooth” Microspar

Molar-tooth (MT) microspar is a volumetrically significant, globally distributed carbonate fabric that occurs almost exclusively in Mesoproterozoic and early Neoproterozoic shallow marine successions. It occurs as uniform, equant crystals, averaging 9 –15 μm in diameter (Figure 1), that characteristically fill MT structures—interconnected networks of spheroidal, spindle, and ribbon-shaped voids that formed within unlithified sediment in shallow, subtidal environments. Cathodoluminescence (CL) analysis of MT microspar reveals two chemically distinct phases: a dully luminescent spheroidal core enclosed by a luminescent, polygonal rim. Crystal size distribution analysis of MT microspar indicates spontaneous nucleation, rapid growth and varying degrees of recrystallization by Ostwald ripening, followed by precipitation of overgrowth cements. Petrographic and isotopic characteristics suggest MT microspar is a primary precipitate and not a diagenetic or neomorphic phenomenon and that precipitation occurred in active communication with Proterozoic seawater. Therefore, constraining the genesis of MT microspar is critical to understanding the geochemical evolution of Proterozoic seawater. Morphological similarities have led to comparisons between MT microspar and experimentally precipitated vaterite, a metastable CaCO3 polymorph. Presented here are results of precipitation experiments designed to investigate the plausibility of vaterite as the precursor mineralogy to MT cores, and to explore the geochemical conditions under which MT microspar may have formed. Any hypothesis for the formation of MT microspar must account for the crystal size and morphologies observed in MT microspar cores, as well the volume of precipitate needed to fill and stabilize MT structures. These experiments show that (1) spheroidal morphologies are common in both vaterite and calcite, suggesting that MT microspar may have initiated as a polymineralic precipitate and (2) that even under greatly elevated saturations, insufficient precipitate is produced to account for observed volumes of MT microspar. Experiments performed at elevated pH with added Mg2+, however, produced a viscous colloid, suggesting that under conditions of high carbonate saturation an amorphous phase of significant volume may have filled, and thus stabilized, MT structures in the unlithified substrate

Cystic fibrosis associated with Wernickes encephalopathy in an older adult.

Here we report the first case of an association between cystic fibrosis and Wernickes encephalopathy. The patient had a history of cystic fibrosis diagnosed in her early 60s associated with pancreatitis and chronic lung disease. She presented with a traumatic hip fracture requiring operative repair. On examination, she was found to have bilateral nystagmus. MRI revealed enhancement of the mammillary bodies. Laboratory results were notable for thiamine deficiency, which in context of the radiographic and physical examination findings, confirmed a diagnosis of Wernickes encephalopathy. The cause of her low thiamine was thought to be poor dietary intake, weight loss and malabsorption associated with exocrine pancreatic insufficiency in the setting of a history of recurrent pancreatitis. The patient had complete resolution of her symptoms with the initiation of thiamine supplementation and pancreatic enzymes. Although classically associated with fat soluble vitamin deficiencies, there are increasing reports of water-soluble vitamin deficiencies associated with cystic fibrosis

The Potential Implications of the Medicare Advantage Stars Methodology for Plans Serving Low Socioeconomic Status Communities

Medicare Advantage (MA) now serves nearly one-third of all Medicare beneficiaries. Many MA participants have low socioeconomic status (SES). The Affordable Care Act (ACA) modified the five-star quality measurement program applied to MA plans (“Medicare stars”) imposing substantial financial incentives and penalties based on plan performance. This study uses a mixed methods approach to examine (1) whether and how serving low-SES participants impact an MA plans’ ability to achieve high Medicare stars scores, (2) whether plans are using enhanced and supplemental benefits to offset SES-related barriers to high performance under the Medicare stars program, and (3) changes policy makers should consider to offset SES-related barriers to high-quality performance under the Medicare stars program. Thirty key informants were interviewed in phase one. Each expressed support, often qualified, for the Medicare Stars program. Each concurred that beneficiary SES factors impact the level of effort required of MA plans to achieve a high Medicare stars scores. They identified a number of specific SES factors that form barriers to high-quality performance and an array of recommended policy changes designed to acknowledge and to offset those barriers. Phase two uses a multivariate analysis of publicly available plan filing data for the years 2014 and 2015 to examine the effect of the percentage of low-income subsidy (LIS) eligible beneficiaries and the level of deprivation in the county in which the plan was offered on the inclusion of benefits and plan design features identified by phase one respondents as likely to offset SES-related barriers to quality care. Neither the percentage of LIS-eligible membership nor county-level deprivation were consistently found to be significantly associated with the inclusion of any of the studied benefits, other than supplemental meals. Designation as a Special Needs Plan (SNP) was significantly associated with the inclusion of nearly all of the studied benefits. In phase 3, five of the phase one respondents participated in follow-up surveys and interviews to evaluate the policy recommendations most commonly made by the phase 1 key informants. Those recommendations form the basis for the plan for change presented in the final chapter.Doctor of Public Healt

Physical Activity Inclusion in Dementia-Friendly Communities: A Mixed Methods Study

© 2024 The Authors. Published by Human Kinetics, Inc. This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0International License, CC BY 4.0. See: http://creativecommons.org/licenses/by/4.0.Dementia-friendly communities (DFCs) are a policy-endorsed approach to community engagement in England that promotes social inclusion to enable people affected by dementia to live well. Research suggests that physical activity is beneficial in encouraging social connection and improving health. A mixed method sequential study design in England involving a national survey (n = 31) and semi structured interviews (n = 65) in three DFCs was carried out. The aim was to understand how DFC senable people affected by dementia to participate in physical activities. An evaluation framework for DFCs was used to organize and interpret the data, and analysis was informed by the inclusive (social) citizen lens. Findings showed that DFCs offered a range of adapted dementia-inclusive and dementia-specific activities; however, people were not routinely offered information at time of diagnosis. Local authorities (councils) were key to enable access to information and infrastructure change to support sustainable inclusion within their local community.Peer reviewe

A Model of Student Learning: A Cross-Disciplinary Examination of Student Reflections of Service-Learning Experiences

The purpose of this study was to measure and analyze student service and engaged learning outcomes employing the qualitative tradition of phenomenology. This study was based on the “Five R” service and engaged learning framework. The population for this project included 565 students enrolled in sixteen different course sections (eight distinct classes) taught by twelve faculty members across six academic departments in three colleges/schools on the campus of a regional teaching university in the Intermountain West. The results yielded support for each “R” in the framework (reciprocity, reflection, rewards of synergy, responsibility, and reality), thereby supporting the validity of the framework across disciplines