Browsing by Subject "stress"
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Item Analysis of Yeast Genes Influencing the Lethality of DNA Damage Related Checkpoint Mutants(2009-05-01) Kim, Eunmi; Siede, WolframThe purpose of this study was to determine the functions of Hug1 and Srl3. It has been reported that HUG1 or SRL3 deletion rescues the lethality of a DNA damage checkpoint gene deleted mutant, mec1Δ. It is known that the lethality of mec1Δ can be rescued by high dNTP levels. To elucidate the functions of these proteins, the phenotypes of hug1Δ and srl3Δuvs, as well as the transcript profile of hug1Δ were analyzed. Novel phenotypes of hug1Δ were uncovered: resistance to oxidative stress or heat shock, earlier arrest in G1/G0 phase, defect in hydroxyurea-induced filamentation, and slow growth inresponse to combined stresses of hydroxyurea and reduced dextrose content. These phenotypes correlate with a transcription profile that indicated altered stress responses in hug1Δ as compared to WT. We assumed that the reason for many constitutively expressed stress-related transcripts is a higher dNTP level in hug1Δ compared to WT. The similarities in the phenotypes of dif1Δ and sml1Δ to those of hug1Δ support the assumption. The phenotypes of dif1Δ and sml1Δ were studied since Dif1 and Sml1 are known inhibitors of ribonucleotide reductase activity. Furthermore, Dif1, Sml1, and Hug1 are considered proteins that evolved from the same ancestor protein. Initially, Srl3 was a protein of special interest because the commercially available srl3Δ mutant causes high spontaneous mutation rates and sensitivity to UV light. However, during the course of this study, it was found that the two phenotypes originated from a second, unrelated mutation in srl3Δ strain. Through complementation test and sequencing, this mutation was identified as a nonsense mutation of MMS2, a gene involved in post-replication repair.Item Building resilience with heart rate variability biofeedback (HRVB): a randomized controlled trial of HRVB to reduce emotional exhaustion/burnout in emergency department and intensive care unit providers(2020-05) Cortez-Neavel, Geordi R.; Jones, Harlan P.; Mathew, Stephen O.; Gatch, Michael B.; Powers, Mark B.; Warren, Ann MarieCortez-Neavel, Geordi, Building Resilience with Heart Rate Variability Biofeedback (HRVB): A Randomized Controlled Trial of HRVB to Reduce Emotional Exhaustion/Burnout in Emergency Department and Intensive Care Unit Providers. Master of Science in Clinical Research Management, November, 2019, 89 pp., 12 figures, 14 tables, journal entries, references, # titles. PURPOSE: The purpose of this study was to compare perceived emotional exhaustion (assessed through MBI, CD-RISC, PSS, and PHQ-2) between two subject cohorts who received interventions designed to reduce emotional exhaustion through utilization of a Heart rate Variability Biofeedback device, its partner app, and paired technique. We sought to evaluate the effectiveness of HRVB as a means to reduce emotional exhaustion as experienced by emergency and trauma care providers in a single-site, hospital setting (ED and ICU). HYPOTHESIS: The daily use of the HeartMath® HRVB device, Inner Balance application, and Quick Coherence technique over a 4-week period decreases emotional exhaustion in emergency and critical care providers. DESIGN: Providers (RN, PA, NP, MD/DO) working in Baylor University Medical Center's emergency department and intensive-care units participated in a 10-week study, consisting of a 4-week randomized control trial followed by a transition week and additional 5-week study "crossover" extension. RESULTS and CONCLUSIONS: Without the sample size to achieve the desired power of this study, no statistically significant conclusions can be drawn at this time. As of the writing of this thesis, the study is still ongoing, and, thus, new participant data may be included as a result of their completion of the RCT portion.Item The Effects of Lifelong Glutathione Deficiency on Functional Decline and Redox Signaling(2018-08) Mock, J. Thomas; Sumien, Nathalie; Forster, Michael J.; Salvatore, Michael; Yang, Shaohua; Zode, Gulab S.Purpose: A recent paradigm shift has implicated redox state as a potential key determinant underlying the aging process. Specifically, a pro-oxidizing shift in the ratio of reduced to oxidized glutathione (key substrate in redox status) is hypothesized to disrupt cellular signaling leading to functional impairments and mortality. Chronic glutathione deficiency is achieved by global knockout of glutamate-cysteine ligase modifier (GCLM), an enzyme subunit at the rate-limiting step in glutathione synthesis. Glutathione levels in GCLM-/- mice are 10-30% of those in GCLM+/+ mice. Our hypothesis stated that diminished glutathione synthesis would be sufficient to produce an accelerated, aging-like pattern effect on function, a shortened lifespan, and negative alterations in redox state. Methods: We characterized GCLM+/+ and GCLM-/- male and female mice with a functional battery (n = 15-23 / sex / age / genotype) measuring motor, cognitive and affective function. We also measured redox state, inflammation, metabolism and autophagy markers in central and peripheral tissues (n = 3-6 / group) at 5, 10, or 20 months of age. Lastly, survivorship and body weights were recorded for all animals (n = 455). Results: Overall, age-related declines in function were observed in all functional tests. In young and adult mice glutathione deficiency did not negatively affect function, rather it decreased anxiety-related behavior, improved coordinated running performance in young females and adult males, and delayed general motor decline in both sexes. In old mice, glutathione deficiency improved balance in males and worsened age-related motordecline in females, yet it had no negative effects on cognition in either sex. Lifespan was also extended in male and female GCLM-/- mice (median and maximum). Lastly, GCLM-/- had reduced liver redox state throughout life but only at 5 months in the young, and had increased inflammatory markers in old mice. Discussion: These data imply that (i) motor and cognitive domains appear to be differentially affected by glutathione deficiency and led to benefits in young/adult GCLM-/- mice, (ii) functional and biochemical outcomes were sexually dimorphic, (iii) glutathione deficiency did not decrease lifespan, but rather extended lifespan, and (iv) redox state was impaired in GCLM-/- mice across the lifespan peripherally, but primarily only at 5 months in central tissues. These data do not support the redox stress hypothesis of aging and require further investigation of the beneficial outcomes associated with chronic glutathione deficiency.Item The Impact of Travel Stressors on the Pathogenesis of Autoimmunity in Female Lupus Mice(2022-05) Dinh, Viet Q.; Mathis, Keisa W.; Ma, Rong; Cunningham, J. Thomas; Basha, RiyazPreliminary studies found that an established model of systemic lupus erythematosus, the female NZBWF1 mouse, developed heightened disease severity later in life when shipped to UNTHSC during summer due to travel stressors. We hypothesized that this was partly due to early life stress that the mice experienced, and that eliminating these stressors will attenuate disease severity. We measured biomarkers of disease severity in NZBWF1 mice that were shipped as adults and compared with mice that were shipped in early life along with mice that were not shipped at all. We found that long-term biomarkers were higher in adult travel mice compared to early life travel mice, that these biomarkers were higher in summer mice compared to winter mice, and that non-travelling mice had the highest levels. Our findings indicate that adulthood stress exacerbates disease progression in NZBWF1 mice, and that seasonal factors impacted lupus pathogenesis in these adult mice.Item The Neuroprotective Efficacy of Antioxidants Against In Vitro Models of Oxidative Stress and Their Theoretical Application Via Intravitreal Injection Encapsulated in Nanoparticles(2010-05-01) Ondricek, Amber J.; Jamboor VishwanathaThe purpose of this study was to explore the possibility of utilizing antioxidants to mitigate oxidative stress induced apoptosis related to neurodegenerative diseases such as glaucoma. Our hypothesis is that in diseases related to an imbalanced redox status, whatever the primary cause may be, the loss of function may be prevented by antioxidants at the level of alleviating oxidative burden and preventing apoptotic signaling events. Application of these antioxidants to the site of injury can be improved using nanoparticle delivery methods. We have done work to characterize a model of mitochondrial associated oxidative stress induced cell death and obtained neuroprotective profiles on a group of antioxidants using this model. We have found that estrogens and phytoestrogens, as well as thiol containing antioxidants, function well as neuroprotectants in our in vitro model. Nanoparticle delivery of these models is a promising intervention and we therefore did work to optimize the characteristics of encapsulating one of these antioxidants, N-acetyl cysteine, in Poly(lactic-coglycolic acid) nanoparticles, which can be localized to the retina. Intravitreal injection of these particles is the preferred delivery route to retinal cells and has not been fully explored. We provide evidence to suggest that the intravitreal injection of nanoparticles is not detrimental to an animal’s vision. Taken together, the results of our experiments suggest that antioxidants remain a promising intervention in diseases related to mitochondrial associated oxidative stress, and that these drugs, when encapsulated in nanoparticles, can be delivered to the retina via intravitreal injection without deleterious side effects.Item Women & Stress: Investigating the Female Stress Syndrome(2006-05-01) Oden, Melissa Standord; Sue LurieOden, Melissa Stanford, Women & Stress: Investigating the Female Stress Syndrome. Master of Public Health (Community Health), May 2006, 47 pp., bibliography. Research indicates that women experience long-term effects of stress that appear to be not only different from, but possibly more harmful than the long-term effects of stress in men. This situation creates the possibility of more chronic illness for women as well as the possibility for higher mortality rates. The purpose of this project is to investigate the effects of stress on professional women in Tarrant County based on meanings and interpretations women give to the stress they experience. It will also provide additional information about the effects of Female Stress Syndrome to contribute to the research literature on this topic.