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  • 1. Toennies, Marc Effect of cryptorchidism on testicular 5 alpha-reduced androgen formation and hypothalamo-hypophyseal secretions in the adult male rat.

    Master of Science, The Ohio State University, 1978, Graduate School

    Committee: Not Provided (Other) Subjects:

  • 2. Harden, Rebekah THE EFFECTS OF LEPTIN ON BONE DEVELOPMENT AND GROWTH IN ZEBRAFISH (Danio rerio)

    Master of Science, University of Akron, 2024, Biology

    LeptinA-F0 knockout Danio rerio were generated using Crispr/Cas9 to test the effects of leptin expression on bone development and growth into adulthood. Within one clutch, 3 mutants were generated for a 25% successful-mutation rate. Using calcein staining and fluorescence microscopy, calcium deposition in vertebrae #3-5 was measured at days 12 and 17 post-fertilization (dpf). Results showed faster calcification rates in leptinA mutants compared to wildtype. Mutants exhibited decreased weight and shorter longitudinal length at onset of adulthood. MicroCT analysis revealed smaller vertebral column volumes per body length in mutants, with individual pre-caudal vertebrae showing no significant difference in volume between mutants and wildtype. Mutant bone density was lower than wildtype. Otoliths showed no significant differences in volume nor density. These findings suggest leptin influences bone remodeling early in vertebral body formation, with effects varying among bones.
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    Committee: Richard Londraville (Advisor); Qin Liu (Committee Member); Rachel Olson (Committee Member) Subjects: Biology

  • 3. Basom, Rose Bone, Brain, and Behavior: Examining the Effects of Acetylcholine Within the Neuroskeletal Relationship

    PHD, Kent State University, 2024, College of Arts and Sciences / School of Biomedical Sciences

    Many neurochemicals that affect social behavior also play a role in mediating bone development and metabolism. In primates, higher levels of neuropeptide Y and serotonin in humans and chimpanzees, compared to monkeys, are associated with decreased levels of aggression and increased social competence, respectively. Additionally, apes have higher levels of acetylcholine (ACh) and lower levels of dopamine, corresponding to internally driven and autonomous social behavior. Humans, conversely, have relatively low ACh and high dopamine, corresponding to externally driven social behavior and social conformity. ACh is specifically associated with the control of internally versus externally motivated behaviors in the striatum and is also known to promote osteoblastogenesis, bone formation, and to also inhibit bone resorption. However, the relationship between neurochemicals in the brain, bone, and behavior has, to date, remained relatively unexplored. In this dissertation, I investigate potential relationships among ACh concentrations and bone architecture by examining rats of differing levels of domestication and also among primates. I show that, in wild-caught and laboratory-raised rats, skeletal ACh concentrations, trabecular spacing, cortical bone density, and cortical area are lower in laboratory-raised rats, while bone volume is higher. Additionally, skeletal ACh may account for 40.8% of variation in trabecular spacing and 35.5% of variation in bone volume among rats. Though the difference in skeletal ACh among groups was consistent with expectations, our other findings largely contrast with currently available literature, warranting further research into the relationship between skeletal and neural ACh. I also show that, while in a highly limited primate sample, there is no relationship between skeletal and neural ACh concentrations, the methods used to explore this relationship could be used in future studies. Lastly, I show that in exploring the relationship between (open full item for complete abstract)
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    Committee: Claude Owen Lovejoy (Committee Chair); Colleen Novak (Committee Member); Richard Meindl (Committee Member); Mary Ann Raghanti (Committee Member) Subjects: Anatomy and Physiology; Biology; Biomedical Research; Developmental Biology; Endocrinology; Evolution and Development; Morphology; Neurobiology; Physical Anthropology

  • 4. El Sanadi, Caroline DEVELOPMENT AND VALIDATION OF CLINICAL PREDICTION TOOLS FOR AIDING IN SELECTION OF 2ND LINE THERAPIES ADDED TO METFORMIN IN TREATMENT OF TYPE 2 DIABETES

    Doctor of Philosophy, Case Western Reserve University, 2020, Epidemiology and Biostatistics

    The overall purpose of this project was to determine and develop clinical tools that aid in medical decision-making for clinicians and their patients when they are faced with decisions regarding which 2nd-line therapy to add on to metformin monotherapy. Outcomes-based approaches were used as they provide clinically meaningful touchpoints for clinicians, and helpful discussion points for patients. It was hypothesized that such tools developed using large data sets and rigorous evaluation methods would perform better at predicting likelihood of certain outcomes than chance or random guessing would, and that these tools could prove useful to clinicians in using evidence to aid and streamline the decision process. The first tool was created to evaluate the likelihood of developing the five most common outcomes for persons with type 2 diabetes when a 2nd-line therapy is added to metformin monotherapy. The hypothesis was correct; the tool demonstrated strong discriminative ability and performed well on standard prediction model evaluations. The second project compared the impact of adding a 2nd-line of either GLP-1RA or DPP-4i on developing a 3-Point MACE outcome. It was hypothesized that, given the large size of the study dataset, results predicting 3P-MACE outcome would be comparable to those observed in many of the recent large cardiovascular outcome trials (CVOTs), however, unlike what was observed in the CVOTs, the study demonstrated no significant difference between drug classes with respect to development of the 3P-MACE outcomes. Future research will include additional validation studies with external validation, implementation studies, and further development of the tool for clinical use.
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    Committee: Douglas Einstadter MD, MPH (Committee Chair) Subjects: Endocrinology; Medicine

  • 5. Kruse, Colin Data-Enabled Approach to Characterize Dynamic Regulatory Pathways in Two Kingdoms

    Doctor of Philosophy (PhD), Ohio University, 2019, Molecular and Cellular Biology (Arts and Sciences)

    The advent of RNAseq has reshaped agriculture, personalized medicine, and the whole of molecular biology. The shared nature of RNA from species to species makes the execution of RNAseq nearly indiscernible between species. While technical aspects of RNAseq analysis have been solved, there is a massive underutilization of data due to the absence of analysts with depth of biological knowledge or biologists with a depth of computational knowledge. Ultimately this results in underutilized data and missed discoveries. By developing new and innovative analytical approaches we can more completely interpret the massive amount of data provided by a single or collective group of RNAseq experiments. To explore the potential of RNAseq, (a) classical interpretation of RNAseq data (Chapter 2) (b) the integration of global metadata and previous literature (chapter 3), (c) the intersection of multiple RNAseq datasets (Chapter 4), (d) clustering analyses to identify coexpression of genes across dissimilar tissues (Chapter 5), and (e) the integration of epidemiological and validation datasets to drive novel analyses of publicly available data (Chapter 6) are applied to variable datasets. Each approach is demonstrated as a successful and broadly applicable approach depending on the research question.
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    Committee: Sarah Wyatt PhD (Advisor); John Kopchick PhD (Advisor); Zhihua Hua PhD (Committee Member); Mark Berryman PhD (Committee Member) Subjects: Bioinformatics; Biology; Molecular Biology

  • 6. Courtney, Ya'el The Production and Localization of Luteinizing Hormone in the Brain

    BS, Kent State University, 2019, College of Arts and Sciences / Department of Biological Sciences

    Luteinizing hormone (LH) is a gonadotropin that has long been known to trigger ovulation in females and testosterone production in males. In recent years it has been found that LH also has notable action in the central nervous system. It has been suggested that LH may be a significant factor modulating cognitive status and Alzheimer's disease pathology. In fact, LH down-regulation has been shown to successfully improve ovariectomy-associated cognition and spine density loss in a mouse model of post-menopausal cognitive deficits. This suggests that LH plays an important role in learning and memory as well as neuroplastic processes. While researchers have begun to understand some of the effects LH has in the brain, much remains to be explored. This study seeks to characterize the production and localization of LH by in-situ hybridization in the mouse brain. Furthermore, single cell RNA sequencing data were used to identify what type of neurons are responsible for producing LH in specific regions of interest and consider possible mechanisms of LH involvement in plasticity. Utilizing these two independent approaches, LH RNA was identified in several brain regions where LH protein has previously been identified. Importantly, this suggests that local LH production is possible in the hypothalamus, hippocampus, amygdala, and cortex. Furthermore, there are differences in LH RNA abundance in select regions between male and female mice and between ovariectomized and control mice. Endogenous production of CNS LH has tremendous implications for the role of independent LH signaling in the brain, and is an important step towards understanding the mechanism by which it modulates cognitive status.
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    Committee: Gemma Casadesus Ph.D (Advisor); Wilson Chung Ph.D (Committee Member); Joel Hughes Ph.D (Committee Member); Timothy Meyers Ph.D, MSN, RN (Committee Member) Subjects: Bioinformatics; Biology; Cellular Biology; Neurobiology; Neurosciences

  • 7. Weigand, Nicole Ecological and Physiological Effects of Proximity to Roads in Eastern Box Turtles (Terrapene carolina carolina)

    Master of Science (MS), Ohio University, 2018, Biological Sciences (Arts and Sciences)

    Roads are ubiquitous in the United States, and their ecological effects are conspicuous. Turtles are among the vertebrate taxa most affected by roads because of their low vagility and use of road and road-side habitats. In 2013, Wayne National Forest in southeastern Ohio was bisected by a new highway, affecting a road-naive population of eastern box turtles (Terrapene carolina carolina), a species of concern in Ohio and vulnerable throughout its range. The goal of this study was to evaluate ecological, physiological, and behavioral effects of proximity to this new road in this road-naive population of turtles. We used a control-impact study to evaluate potential ecological and physiological effects of proximity to roads, employing radio-telemetry to assess space use, movement behavior, and habitat selection. We used novel bioassay techniques to analyze indicators of chronic stress (across the prior several months) using corticosterone stored in nail keratin. Overall, we found no significant differences in home range sizes, habitat preferences, or corticosterone concentrations between road-side and control sites. While our work suggests that proximity to roads has limited indirect influence on the ecology and chronic stress responses of eastern box turtles, and that road-naive turtles demonstrated avoidance of a high-traffic highway, the road network likely continues to contribute to population declines through direct mortality, and further inquiry is needed to assess road effects, particularly in the areas of stress endocrinology and impacts on demography.
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    Committee: Viorel Popescu (Advisor) Subjects: Animal Sciences; Animals; Biology; Conservation; Ecology; Endocrinology; Wildlife Conservation; Wildlife Management

  • 8. Edes, Ashley Assessing Long-Term Stress in Great Apes: Allostatic Load in Western Lowland Gorillas (Gorilla gorilla gorilla)

    Doctor of Philosophy, The Ohio State University, 2018, Anthropology

    Stress-centered research in primates has taken many forms (e.g., predation, dominance hierarchies, habitat fragmentation, social support), using both behavioral and physiological responses to characterize effects of stressful events and illuminate the consequences of those experiences. Because stress responses induce changes across systems that are non-linear and may be dissociated, it is important single biomarkers are not used to infer soma-wide physiological responses. However, holistic physiological measures which simultaneously incorporate stress-induced alterations throughout the soma are underdeveloped. Clinical research in humans has addressed this issue. Over time, damage from stress accumulates, causing physiological dysregulation known as allostatic load. Allostatic load may eventually lead to chronic degenerative conditions and shortened lifespan. Based on allostatic load theory, allostatic load indices (ALIs) were developed to assess current allostatic load and predict risk of future morbidity and mortality. For the past two decades, the predictive capacity of ALIs were applied only to humans. However, stress responses are conserved among primates and great apes share with us behavioral and genetic similarities while also developing the same chronic degenerative conditions. Connecting humans and nonhuman primates, my research developed the first nonhuman ALIs and applied them to one of our closest relatives, western lowland gorillas. The first objective was to determine predictors and outcomes of allostatic load by verifying and extending pilot study results. This was done by increasing sample size and then testing hypotheses of potential predictors and outcomes of allostatic load. Age, parity, birth cohort, and rearing history were observed to be robust predictors of allostatic load. Some analyses also showed support for sex and stressful events, both total and by type, as predictors of allostatic load. In turn, allostatic load was associated wi (open full item for complete abstract)
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    Committee: Douglas Crews (Advisor); Debra Guatelli-Steinberg (Committee Member); W. Scott McGraw (Committee Member); Barbara Wolfe (Committee Member) Subjects: Animal Diseases; Animal Sciences; Animals; Endocrinology; Health; Neurobiology; Welfare; Wildlife Conservation; Wildlife Management; Zoology

  • 9. Kane, Erin Socioecology, stress, and reproduction among female Diana monkeys (Cercopithecus diana) in Cote d'Ivoire's Tai National Park

    Doctor of Philosophy, The Ohio State University, 2017, Anthropology

    Socioecological models have been used to explore the relationship between female sociality and feeding ecology for nearly 40 years. Models typically distinguish between species eating ubiquitously distributed resources (e.g., leaves) in which females do not exhibit strong social bonds, engage in minimal feeding competition, and minimal territorial defense. These are contrasted with species relying on patchily distributed resources (e.g., ripe fruit) in which females do exhibit social bonds, engage in feeding competition, and defend group territories. Although these models have been critiqued and extended, these basic predictions have been widely used to develop hypotheses about the relationship between ecology and sociality among primates. Much of this research has focused on open-habitat and/or terrestrial primates, while relationships between ecology and sociality remain unexamined in many forest-dwelling and/or arboreal taxa. This is detrimental to our ability to develop unifying models of primate sociality and ecology, and problematic considering the arboreal, forest-dwelling niche filled by the earliest primates and primates in their evolutionary environment. This dissertation examines the relationship between ecological variables and diet, social behavior, reproduction, and stress in arboreal, forest-dwelling guenons. Previous research has demonstrated that Diana monkeys (Cercopithecus diana) exemplify many predictions of socioecological; models: they are ripe fruit specialists, females are philopatric and socially bonded, and feeding competition both within and between groups is relatively high compared to closely related taxa. Here, I use socioecological data collected between July 2013-August 2015 on habituated adult female Diana monkeys living in the Tai Forest, Cote d'Ivoire, and fecal samples collected over the same period to test the hypothesis that fluctuations in food availability have significant consequences for Diana monkeys in terms of their d (open full item for complete abstract)
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    Committee: W. Scott McGraw PhD (Committee Chair); Debra Guatelli-Steinberg PhD (Committee Member); Dawn Kitchen PhD (Committee Member); Barbara Piperata PhD (Committee Member) Subjects: Biology; Ecology; Physical Anthropology; Zoology

  • 10. Skelley, Dean The effects of estradiol-17β on in vitro bovine steroidogenesis /

    Doctor of Philosophy, The Ohio State University, 1966, Graduate School

    Committee: Not Provided (Other) Subjects: Biology

  • 11. Gass, George The endogenous and exogenous metabolism of adrenal, pituitary, and thyroid tissues of male rats following prolonged treatment with testosterone propionate /

    Doctor of Philosophy, The Ohio State University, 1955, Graduate School

    Committee: Not Provided (Other) Subjects: Biology

  • 12. Jackson, LaDonya Type 1 Diabetes Diagnostic Assay

    Master of Science (MS), Ohio University, 2015, Biomedical Engineering (Engineering and Technology)

    The objectives of this thesis research project were to (i) develop an assay sensitive enough to detect dead or dying pancreatic beta cells and to (ii) use this assay to predict which at-risk individuals will go on to develop T1DM. In vitro and in vivo approaches were utilized for its validation. This novel assay differentiated between beta cells and non-beta cells with higher analytical and diagnostic sensitivity than previous approaches. With the novel application of mathematical models the assay was also able to retrospectively predict which at-risk individuals would go on to develop T1DM with high sensitivity and specificity. This assay has the potential to be applied alone or in combination with islet antibodies to identify individuals in the very early stages of T1DM to allow for earlier intervention and perhaps halt beta cell destruction and thus prevent this disease.
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    Committee: Kelly McCall (Advisor); Frank Schwartz (Advisor); Doug Goetz (Committee Member); Monica Burdick (Committee Member); Calvin James (Committee Member) Subjects: Biology; Biomedical Engineering; Biomedical Research; Medicine; Molecular Biology

  • 13. Rudinsky, Adam Pharmacology of the GLP-1 analog exenatide extended-release in healthy cats

    Master of Science, The Ohio State University, 2015, Comparative and Veterinary Medicine

    Exenatide extended-release (ER) is a microencapsulated formulation of the GLP-1-receptor agonist exenatide. It has a protracted pharmacokinetic profile that allows a once-weekly injection with comparable efficacy to insulin and an improved safety profile in type-2 diabetic people. Here we studied the pharmacology of Exenatide-ER in 6 healthy cats. A single subcutaneous injection of Exenatide-ER (0.13 mg/kg) was administered on day 0. Exenatide concentrations were measured for 12 weeks. A hyperglycemic clamp (target = 225 mg/dL) was performed on days minus 7 (Clamp-I) and 21 (Clamp-II) with measurements of insulin and glucagon concentrations. Glucose tolerance was defined as the amount of glucose required to maintain hyperglycemia during the clamp. Continuous glucose monitoring (CGM) was performed on weeks 0, 2 and 6 post-injection. Plasma concentrations of exenatide peaked at 1 hour and 4 weeks post-injection. Comparing Clamp-1 to Clamp-2, fasting BG decreased (mean [±SD] = -11 ± 8 mg/dL, P = 0.02), glucose tolerance improved (median [range] +33% [4-138%], P = 0.04), insulin concentrations increased (+36.5% [-9.9-274.1%], P = 0.02) and glucagon concentrations decreased (-4.7% [0-12.1%], P = 0.005). Compared to pre-injection values on CGM, glucose concentrations decreased and the frequency of readings < 50 mg/dL increased at 2 and 6 weeks post-injection of Exenatide-ER. This did not correspond to clinical hypoglycemia. No other side effects were observed throughout the study. Exenatide-ER was safe and effective in improving glucose tolerance 3 weeks after a single injection. Further evaluation is needed to determine its safety, efficacy and duration of action in diabetic cats.
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    Committee: Chen Gilor (Advisor); Christopher Adin (Committee Member); Ramiro Toribio (Committee Member); Valerie Parker (Committee Member) Subjects: Medicine; Pharmacology; Veterinary Services

  • 14. Baldwin, Jeffrey Determination of a Two-Week `Window’ for PCB Influence on Ultrasonic Vocalization and Other Behavioral Measures in Young Sprague-Dawley Rats

    Master of Science (MS), Bowling Green State University, 2014, Biological Sciences

    Incorporation of polychlorinated biphenyls (PCB) in the diet of pregnant rats has been shown to disrupt the thyroid status of offspring, as well as their behavior. In an effort to determine a two-week `window’ in which PCB exposure is most influential in development, pregnant dams were fed a control mash diet, and treatment groups were fed a mash diet containing equal amounts of PCB 47/77 (totaling 25 ppm of PCB) during a specific two-week interval of the gestational and/or lactational period. Rat pup behavior was tested on postnatal day (PND) 3 (isolation ultrasonic vocalizations, USVs), PND 7 (isolation USVs), PND 14 (grooming behavior), PND 21 (open field behavior), and PND 22 (play behavior). Serum thyroxine (T4) and triiodothyronine (T3) concentrations were determined on each testing day except PND 22. PCB significantly depressed serum thyroid hormone concentrations in a predictable fashion; T4 was significantly depressed in rat pups exposed to PCB, and it was more pronounced on each testing day by pups both currently and most recently exposed. On PND 3, mean serum T4 in pups exposed during gestational week 3 and lactational week 1 (GW3/LW1) was depressed the most (39% less than controls), followed by that of pups exposed during later gestation (GW2/3) (30%). On PND 7, a significant depression was found in pups exposed during LW 1/2 (37%). On PND 14, pups exposed during both `windows’ LW1/2 and LW2/3 showed depressed T4 levels (37% and 32%, respectively). No significant depressions were observed on PND 21; however, the T4 depression of pups in group LW2/3 nearly reached statistical significance (24%, p = 0.06). Mean serum T3 concentrations were also depressed in response to PCB exposure, but not at a significant level. The number of isolation USVs emitted by pups exposed to PCB during `windows’ GW1/2, GW2/3, and GW3/LW1 were elevated on both PND 3 (11%, 25%, and 22%, respectively) and PND 7 (11%, 16%, and 21%, respectively) in relati (open full item for complete abstract)
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    Committee: Lee Meserve Ph.D. (Advisor); Howard Cromwell Ph.D. (Committee Member); Michael Geusz Ph.D. (Committee Member) Subjects: Biology; Developmental Biology; Developmental Psychology; Endocrinology; Neurosciences; Psychology; Toxicology

  • 15. Rutherford, Cynthia Cost Effective Analysis of Lifestyle Interventions Versus Standard Treatment In Patients With Type 2 Diabetes: A Literature Review

    MS, University of Cincinnati, 2014, Medicine: Epidemiology (Environmental Health)

    There are 25.8 million children and adults in the United States, 8.3% of them have diabetes. Twenty five point six million, or 11.3 % of all people 20 years or older have diabetes . Type 2 diabetes accounts for 90 to 95% of diabetes cases in the United States . Type 2 diabetes runs in families. In part, this tendency is due to children learning bad habits eating a poor diet, not exercising from their parents; however there is also a genetic basis. Risk factors for Type 2 diabetes include excess body fat, physical inactivity, and smoking. A determination of Body Mass Index (a calculation of your height and weight) will indicate if a person is overweight or obese. The U.S. Department of Health and Human Services indicates that a BMI of 25 to 30 is considered overweight and over 30 is considered obese. With every 1 increase in BMI, the risk of developing type 2 diabetes increases by 10 to 30%1. Diabetes is also the leading cause of kidney failure, nontraumatic lower-limb amputations, and new cases of blindness among adults in the United States. Diabetes is a major cause of heart disease and stroke, and is the seventh leading cause of death in the United States. Diabetes type 2 a serious epidemic in the United States that, with lifestyle interventions, can be reduced. Type 2 diabetes is becoming more common due to increasing obesity and failure to exercise. Diet and exercise are key factors in reducing the amount of body fat, which is a main risk factor in type 2 diabetes. Studies have shown that increased activity and better choices of foods in the diet can reduce or even eliminate type 2 diabetes. The average median annual direct medical costs of non-insulin dependent type 2 diabetes is $1,700 to $2,100 per person with no microvascular, neuropathic, or cardiovascular complications.
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    Committee: Erin Nicole Haynes Dr. P.H. (Committee Chair); Mark Eckman M.D. (Committee Member) Subjects: Epidemiology

  • 16. Fuller, Grace The Night Shift: Lighting and Nocturnal Strepsirrhine Care in Zoos

    Doctor of Philosophy, Case Western Reserve University, 2014, Biology

    Over billions of years of evolution, light from the sun, moon, and stars has provided organisms with reliable information about the passage of time. Photic cues entrain the circadian system, allowing animals to perform behaviors critical for survival and reproduction at optimal times. Modern artificial lighting has drastically altered environmental light cues. Evidence is accumulating that exposure to light at night (particularly blue wavelengths) from computer screens, urban light pollution, or as an occupational hazard of night-shift work has major implications for human health. Nocturnal animals are the shift workers of zoos; they are generally housed on reversed light cycles so that daytime visitors can observe their active behaviors. As a result, they are exposed to artificial light throughout their subjective night. The goal of this investigation was to examine critically the care of nocturnal strepsirrhine primates in North American zoos, focusing on lorises (Loris and Nycticebus spp.) and pottos (Perodicticus potto). The general hypothesis was that exhibit lighting design affects activity patterns and circadian physiology in nocturnal strepsirrhines. The first specific aim was to assess the status of these populations. A multi-institutional husbandry survey revealed little consensus among zoos in lighting design, with both red and blue light commonly used for nocturnal illumination. A review of medical records also revealed high rates of neonate mortality. The second aim was to develop methods for measuring the effects of exhibit lighting on behavior and health. The use of actigraphy for automated activity monitoring was explored. Methods were also developed for measuring salivary melatonin and cortisol as indicators of circadian disruption. Finally, a multi-institutional study was conducted comparing behavioral and endocrine responses to red and blue dark phase lighting. These results showed greater activity levels in strepsirrhines housed under red light (open full item for complete abstract)
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    Committee: Kristen Lukas PhD (Advisor); Mary Ann Raghanti PhD (Committee Member); Patricia Dennis PhD (Committee Member); Christopher Kuhar PhD (Committee Member); Mark Willis PhD (Committee Member) Subjects: Behavioral Sciences; Biology; Endocrinology; Welfare; Zoology

  • 17. Papenfuss, Tracey Sex hormones and dendritic cells: influences on the initiation of the autoimmune disease experimental autoimmune encephalomyelitis

    Doctor of Philosophy, The Ohio State University, 2007, Veterinary Biosciences

    Sex hormones can dramatically modulate immune responses and influence both susceptibility and clinical disease course in autoimmune disease. In multiple sclerosis (MS), sex determines susceptibility and clinical presentation, while pregnancy has profound therapeutic actions over currently approved MS treatments. The objectives of this thesis were to determine the influences of sex hormones on the induction of an immune response using experimental autoimmune encephalomyelitis (EAE). The influence of sex hormones and genetics on EAE was evaluated using multiple mouse strains with different MHC class II haplotypes. We identified a new model of sexually dimorphic EAE and a model for primary progressive multiple sclerosis. Male B10.PL mice had increased clinical severity, mortality and histopathological infiltrates associated with an increased pathogenic Th1 immune response. Additionally, female sex hormones at the time of disease induction are protective, suggesting that sex hormones present at disease induction are important in influencing EAE. Since DCs are uniquely able to drive naive Th0 cell differentiation to shape adaptive immune responses, we evaluated the influence of the pregnancy specific hormone estriol (E3) on DCs and EAE induction. DCs were expanded in vivo in the presence of pregnancy levels of E3. E3 DCs had an “activated regulatory” phenotype (i.e. increased CD80, CD86, PD-L1, PD-L2, B7-H3 and B7-H4), decreased mRNA levels of proinflammatory IL-12, TNF-alpha and NF-kappaB and increased mRNA levels of immunoregulatory IL-10 and IDO. E3 DCs produced less IL-12 and Th0 cells proliferated less in vitro with E3 DCs. Mice receiving E3 DCs were protected from EAE, having decreased severity, decreased CDS and complete resolution of clinical signs compared to mice receiving Pb DCs. This effect is dose-dependent and, importantly, E3 DCs maintain their protective phenotype in the face of potent inflammatory stimuli (i.e. in vitro LPS and in vivo adjuvants). Mice r (open full item for complete abstract)
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    Committee: Caroline Whitacre (Advisor) Subjects:

  • 18. Drummond, Christopher Regulation of Ecdysone 20-Monooxygenase Activity in the Tobacco Hornworm, Manduca sexta and the Apparent Occurrence of this Activity in Ascaris suum (Nematoda)

    Doctor of Philosophy (Ph.D.), Bowling Green State University, 2011, Biological Sciences

    At specific intervals, increased concentrations of two steroid hormones, i.e., ecdysone (E) and 20-hydroxyecdysone (20E), elicit developmental changes in arthropods. Conversion of E to the active molting hormone, 20E, in the tobacco hornworm Manduca sexta is catalyzed by the cytochrome P450-containing ecdysone 20-monooxygenase system (E20M). During embryogenesis, M. sexta E20M activity increased for the first 72 hours at which time it peaked and subsequently significantly declined. The increased activity coincided with the increase of free ecdysteroids and the progression of two embryonic molts. In midgut tissue of fifth instar M. sexta, decreases in second messenger 3',5'cyclic guanosine monophosphate (cGMP) concentration inhibited day five E20M activity, but increases in cGMP concentration restored E20M activity. Midgut cGMP content peaked on day five of the instar in concert with the highest level of E20M activity observed. Molecular studies with midgut tissue demonstrated that the E agonist RH-5849 elicited increases in E20M (the shade gene) expression. In the presence of two guanylate cyclase inhibitors, E20M expression significantly increased. Inhibition remediation by pharmacological means resulted in significantly decreased shade expression. While it is unclear as to where cGMP exerts its effects on E20M activity, the data indicated that the second messenger affected the level of transcription, translation, or enzyme activity either individually or in some combination. Interestingly, E20M activity also was found to be affected by six synthesized anthraquinones suggesting that these compounds can serve to disrupt M. sexta development. Lastly, E20M-like activity was observed in female Ascaris suum (Nematoda) both in muscle and reproductive tissue. Although E20M localization in muscle was unclear, in reproductive tissue E20M activity resided mainly with microsomes. This work provides a number of important insights into the regulation of M. sexta E20M during dev (open full item for complete abstract)
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    Committee: Carmen Fioravanti Ph.D. (Committee Chair); Daniel Pavuk Ph.D. (Committee Member); Lee Meserve Ph.D. (Committee Member); Scott Rogers Ph.D. (Committee Member); Hangfeng Chen Ph.D. (Committee Member) Subjects: Agriculture; Animal Sciences; Animals; Biochemistry; Biology; Cellular Biology; Developmental Biology; Endocrinology; Entomology; Organismal Biology; Parasitology; Physiology