Understanding Addiction, Depression, And Autism Spectrum Disorder Through Structure-Function Analyses Of The Dopamine And Serotonin Transporters

The dopamine (DAT) and serotonin (SERT) transporters are monoamine neurotransmitter transporters (MATs) responsible for the reuptake of dopamine (DA) or serotonin (5-HT) from the synapse following vesicular release, effectively regulating synaptic neurotransmission. Blockade of these transporters by antagonists such as psychostimulant drugs or transporter mutations that affect function can compromise DA or 5-HT homeostasis and impact fundamental brain processes including movement, emotion, behavior, motivation, and memory. To address these issues, my dissertation research focused on: (1) identifying and characterizing the cocaine binding site in DAT, (2) determining the influence of membrane depolarization on DAT trafficking, (3) investigating antidepressant metabolite action in an antidepressant-insensitive mouse model, and (4) understanding the link between the structural and functional changes induced by mutations in SERT associated with autism spectrum disorder. Cocaine binding site in DAT – Through the development and utilization of several high affinity, photoactivatable cocaine ligands we identified a cocaine binding site in the core of DAT, a site that overlaps with the putative DA binding site, supporting a competitive mechanism for cocaine inhibition of DA uptake. (Chapters II-IV) Influence of membrane depolarization on DAT trafficking – Trafficking of mature DAT to and from the cell membrane is a highly regulated process. Within this process, we demonstrated that membrane depolarization alone could induce a CaMKIIα- and dynamin-dependent rapid reversible reduction in membrane DAT. (Chapter V) Characterization of antidepressant metabolites in the blockade of 5-HT reuptake – As studies of the antidepressant selective serotonin reuptake inhibitors (SSRIs) have revealed discrepancies between acute and chronic dosing treatments, we evaluated the sensitivity of SSRI metabolites in a mouse model of depression and identified a role for metabolites in antidepressant administration that may confound study conclusions. (Chapter VI) Autism-associated SERT mutations – Previously, several rare SERT coding variants were identified in humans with autism spectrum disorder that augment 5-HT transport function. We studied the structure of these variants and discovered alterations in SERT tertiary structure, which likely impact the catalytic activity or surface expression of SERT. (Chapter VII

Sagadahoc County Community Food Resources

Food resources found in Sagadahoc County, Maine: Farms - community supported agriculture Farm stands (Harvest Bucks) Farmers\u27 market (EBT) Mobile market Food pantrieshttps://digitalcommons.usm.maine.edu/fsp-sagadahoc/1000/thumbnail.jp

Home schoolers transition to public schools in West Virginia

This study investigated the issues embedded in the transition of home schooled students entering or reentering public school in West Virginia. The research was primarily qualitative, however; quantitative research was also employed. Two rounds of interviews, for a total of 46 interviews, were conducted over an eight month period. The interviews included three families and their children who had been home schooled and were returning to public school. The public school teachers who had the returning students placed in their classrooms were also interviewed. The following questions guided the research: (1) What were the factors that influenced the home schooling family\u27s decision to enter their children in public school? (2) What do home schooling families believe public schools currently do and/or should do to support their children in their transition from home to school? (3) What is the experience that home schooling students have upon entering public schools and what could the public schools do to participate in that experience? and (4) What are the critical issues embedded in the transition from home schooling to public schools for parents, children and educators? Major findings from the study included: (1) A key factor the in home schooling family\u27s decision to enroll their children in public schools was to establish positive social interactions with peers and teachers; (2) Support received by the returning home schooled student from public schools, i.e., classroom teachers, is haphazard and is more apt to be academic rather than emotional support; (3) Public schools need to take an active role in the transition of returning home schooled students; (4) Conferences should be held among public school educators, home schooling parents and students before the child enters public school; (5) The development of positive social relationships by the returning student is key to the successful transition back to public school and (6) Dual enrollment in public school and home school should be considered as an option for students

Synthesis and Analysis of 6-acetyl-1,2,3,4-tetrahydropyridine, a Major Contributor to ‘Mousy’ Off-Flavor in Sour and Wild Beers

Unexpected tastes can negatively impact consumer experience in the beer industry. One such taste, a ‘mousy’ off-flavor, is diminishing the quality of sour and wild beers throughout the brewing community. The unpleasant flavor is a result of the combined presence of three organic compounds: 6-acetyl-1,2,3,4-tetrahydropyridine (ATHP), 2-acetyl-1-pyrroline, and 2-ethyl-3,4,5,6-tetrahydropyridine. Because of its unpredictable nature, brewers must wait for the compound to disappear before distribution, costing them valuable time and revenue. The factors responsible for formation, reasons for persistence, and degradation timelines of the compounds were unknown. A method for quantification was therefore necessary to determine those characteristics, and such quantification depended upon the availability of a pure standard. In response, synthesis protocols, a GC-MS method for qualification, and a method for extraction from beer were developed for ATHP. ATHP was synthesized via a mechanism by which dihydroxyacetone reacts with proline in the presence of sodium bisulfite. The product was synthesized in low yields, so different routes of synthesis were attempted. ATHP product was highly impure as evidenced by GC-MS, so various purification techniques were employed. Extraction protocols were developed on basic profile beers that were spiked with product and progressed to naturally ‘mousy’, complex beers. The ATHP component of the uncontrolled ‘mousy’ off-flavor in was synthesized, identified, and purified

Waldo County Community Food Resources

Food resources found in Waldo County, Maine: Community supported agriculture Harvest Bucks accepted Community resources Food pantrieshttps://digitalcommons.usm.maine.edu/fsp-waldo/1001/thumbnail.jp

International Governance of Oil Spills from Upstream Petroleum Activities in the Arctic : Response over Prevention?

The paper is partly based on the author’s PhD thesis submitted to the University of Aberdeen in 2017. The author is grateful to her supervisors Professor Tina Hunter and Dr Catherine Ng, and her examiners Professor Elizabeth Kirk and Professor Timo Koivurova for their time and comments.Peer reviewedPostprin

A listing of modifications, models, and teaching roles utilized by inclusion teachers at a secondary school

The purpose of this study was to determine which modifications, teaching roles, and responsibilities the regular and special education team teachers use to give support in inclusive secondary classrooms. The co-teachers were asked to make recommendations to improve inclusion program effectiveness. The information was collected through a questionnaire disseminated to seven regular educators and five special educators who team-teach in grades seven to twelve. The percentages of the teachers\u27 responses were reported along with a list of teacher recommendations. The first part of the questionnaire included a checklist of classroom modifications related to classroom organization, instructional methodology, assignment adaptations, testing modifications, and socialization adaptations. The majority of the team teachers use many modifications with the physical organization of the class, instruction, assignments, and testing. Very few inclusion staff utilize social adaptations at this secondary level. Part two of the survey found that the majority of the team teachers share classroom responsibilities such as determining materials, lesson planning, grading, and test development. The third survey section shows an equal use of the team teaching model and support instruction. The final section of the questionnaire asked for recommendations the respondents believed would improve the effectiveness of the inclusion program

Planning and Experiencing the Move to a Continuing Care Retirement

This article suggest that continuing care retirement communities have become more common. While expensive, they offer many amenities as well as long term car