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Full-Text Articles in Medicine and Health Sciences
Creation Of A Mouse With A Humanized Fpgs Gene Compatible With Normal Development, Linying Xie
Creation Of A Mouse With A Humanized Fpgs Gene Compatible With Normal Development, Linying Xie
Theses and Dissertations
Abstract: Folylpoly-γ-glutamate synthetase (FPGS) catalyzes the formation of polyglutamate forms of the reduced folates and antifolates such as methotrexate (MTX) and pemetrexed; this allows the retention of folates and antifolate cancer drugs inside the cell. The enzyme activity of FPGS is essential for cell proliferation and survival. The mouse fpgs gene contains two promoters spaced 10 kb apart which are activated in a tissue-specific manner. The upstream promoter (P1) and exons A1a and A1b are used in some differentiated tissues, mainly liver and kidney, whereas the downstream promoter (P2) and exon 1 are used in rapidly dividing cells. In contrast, …
Identification Of Pharmacological And Molecular Mechanisms Involved In Nicotine Withdrawal, Kia Jackson
Identification Of Pharmacological And Molecular Mechanisms Involved In Nicotine Withdrawal, Kia Jackson
Theses and Dissertations
Tobacco dependence is the leading cause of preventable death in the United States. Despite currently available smoking cessation therapies, there is a high rate of relapse in smoking among those attempting to quit. While the somatic signs of nicotine withdrawal (insomnia, increased appetite, weight gain) contribute to the continuation of smoking behavior, it has been hypothesized that the affective signs (depression, anxiety, craving, irritability) are greater motivators of relapse and continued tobacco use. There are few studies that assess the molecular and receptor-mediated mechanisms of nicotine withdrawal; therefore, our studies focus on identifying the nicotinic acetylcholine receptor (nAChR) subtypes and …
Promotion Of Tumor Cell Death Through The Induction Of, Tuyen Nguyen
Promotion Of Tumor Cell Death Through The Induction Of, Tuyen Nguyen
Theses and Dissertations
Microtubule poisons have proven to be effective in the treatment of a variety of malignancies. Although taxol-based derivatives promote microtubule stabilization, there is continuing interest in compounds that, like colchicines, act as microtubule destabilizing agents. Previous work from this laboratory showed that the novel microtubule poison, JG- 03-14, was active against breast tumor cells, promoting autophagic cell death. In the current work, we studied the influence of JG-03-14 on p53 wild type HCT116 colon carcinoma cells. A crystal violet sensitivity assay indicated that JG-03-14 induced growth inhibition, with 75% suppression of growth evident at a concentration of 500 nM. Time …
Endocannabinoid Modulation Of Spatial Memory In Aversively And Appetitively Motivated Barnes Maze Tasks, John Pinckney Harloe
Endocannabinoid Modulation Of Spatial Memory In Aversively And Appetitively Motivated Barnes Maze Tasks, John Pinckney Harloe
Theses and Dissertations
Genetic deletion or pharmacological blockade of the CB1 receptor has been reported to impair extinction learning in aversive conditioning (i.e., conditioned fear and Morris water maze) paradigms, but not in operant procedures in which food reinforcement is earned. It is difficult to discern whether the differential effects caused by CB1 receptor disruption on extinction result from the hedonics (i.e., aversive vs. appetitive) or is related to the required responses associated with these disparate tasks. In order to evaluate whether the hedonics is the determining factor, we used either aversive (i.e., escape from bright lights and air turbulence) or appetitive (i.e., …
Examining The Behavioral And Molecular Aspects Of Adolescent Nicotine Dependence: Implications For Vulnerability To Drugs Of Abuse, Dena Heath Kota
Examining The Behavioral And Molecular Aspects Of Adolescent Nicotine Dependence: Implications For Vulnerability To Drugs Of Abuse, Dena Heath Kota
Theses and Dissertations
Approximately 200 million men and 100 million women smoke worldwide. In the United States, an estimated 25.9 million men (23.9 percent) and 20.7 million women (18.1 percent) are smokers. The commencement of smoking at a young age is thought to increase addiction liability, decrease the probability of successful cessation, and correlate with a higher number of cigarettes smoked per day. Studies from the World Health Organization indicate that between 80,000 and 100,000 children start smoking every day worldwide. These statistics suggest that adolescence is a critical phase for developing nicotine dependence. The work in this dissertation contributes to the further …