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1
Wentworth, Bruce Martin. "Characterization of the Two Non-Allelic Preproinsulin Genes in Mice: a Thesis." eScholarship@UMMS, 1987. http://escholarship.umassmed.edu/gsbs_diss/290.
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The two non-allelic preproinsulin genes of the mouse have been cloned and their nucleotide sequences determined. The mouse preproinsulin I gene, like its rat counterpart, has only one intron. Homology between the two mouse genes extends in the 5' direction to about position -500. Homology 3' of the coding sequence terminates shortly after the polyadenylation signal with a dA rich region found in gene I.
The coding sequences of the two genes have been compared. The deduced amino acid sequences of the mature hormones are identical to the published protein sequences and to the corresponding sequences of rat insulins I and II. The prepeptides of mouse insulin I and II differ at six positions. However, they maintain hydrophobic cores that are required for transport of the nacent peptide across microsomal membranes. The B-peptide of mouse insulin I differs from insulin II at two positions: at position B9 a proline has replaced a serine, and at position B29 a lysine has replaced a methionine, compared to the sequence of insulin II. The A-peptides of the two hormones are identical. The C-peptide of mouse proinsulin I has a deletion eliminating amino acids C17 (Gly) and C18 (Ala) compared to the sequence of proinsulin II. The presence of this deletion in mature RNA was confirmed through an S1 nuclease assay.
The transcriptional start sites for the preproinsulin genes were determined with S1 and Mung Bean nuclease assays, and with a primer extension assay. The data indicate that transcription of the mouse preproinsulin genes starts 6 bp 5' of the site reported for the rat II gene.
Single-stranded DNA probes were used to determine the structure of the 3' ends of the preproinsulin mRNAs. Hybridization conditions were used which only allowed each probe to detect its cognate mRNA. Digestion of the resulting DNA-RNA duplex molecules with S1 nuclease followed by gel electrophoresis demonstrated that transcription of mouse preproinsulin I mRNA terminates 18 bases after the polyadenylation signal. Transcription of preproinsulin II mRNA terminates 43 bases after the polyadenylation signal, thus extending 25 bases past the last point of homology between the two genes.
The 3' end-specific probes were used in experiments designed to determine the ratio of preproinsulin I and II mRNA in pancreatic extracts of normal, fasted and fasted and refed mice. In all cases the amount of preproinsulin I mRNA exceeded preproinsulin II by about 2.3:1. These results were extended to include an analysis of preproinsulin mRNA from freshly isolated islets and islets incubated for 48 hours in the presence of 2.8 mM or 16.7 mM glucose. With both high and low glucose concentrations, the amount of preproinsulin I mRNA exceeded preproinsulin II by about 2.3:1. The mouse islets were also incubated with 3H-leucine and the ratio of insulin I and II determined after fractionation by HPLC. Unlike the mRNA results, the level of insulin II, within the islets and secreted into the media, exceeded insulin I by about 2:1 under all conditions.
The available preproinsulin prepeptide amino acid sequences have been compared. The sequence of mouse I prepeptide differs from most other insulin prepeptides at amino acid position 4. At that position a tryptophan residue that is conserved in most insulin prepeptides has been replaced by a leucine in the mouse I prepeptide. This change causes a shift in the hydropathy profile in that region of the mouse insulin I prepeptide making it more hydrophobic. Every other insulin prepeptide is relatively hydrophilic at that position. This difference is postulated to interfere with signal recognition particle mediated regulation of translation and/or transport of nacent mouse preproinsulin I to microsomal membranes, and nay account for the discordant mRNA-peptide ratios.
The structure of the insulin genes in a number of myomorph rodents has been examined. The data indicate that only members of the sub-family Murinae have two insulin genes.
2
Hickey, Ashley N. "Expression of CTB-proinsulin in transgenic chloroplasts." Honors in the Major Thesis, University of Central Florida, 2008. http://digital.library.ucf.edu/cdm/ref/collection/ETH/id/1088.
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This item is only available in print in the UCF Libraries. If this is your Honors Thesis, you can help us make it available online for use by researchers around the world by following the instructions on the distribution consent form at http://library.ucf.edu/Systems/DigitalInitiatives/DigitalCollections/InternetDistributionConsentAgreementForm.pdf You may also contact the project coordinator, Kerri Bottorff, at kerri.bottorff@ucf.edu for more information.Bachelors
Burnett College of Biomedical Sciences
Molecular and Microbiology
3
Alaynick, William Arthur. "Phenotypic characterization of estrogen-related receptor gamma mutant mice." Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2006. http://wwwlib.umi.com/cr/ucsd/fullcit?p3235013.
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Thesis (Ph. D.)--University of California, San Diego, 2006.Title from first page of PDF file (viewed December 6, 2006). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references.
4
Chen, Edward. "Genetic modifiers of cerebellar hypoplasia in Zfp423-deficient mice." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2009. http://wwwlib.umi.com/cr/ucsd/fullcit?p1460057.
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Thesis (M.S.)--University of California, San Diego, 2009.Title from first page of PDF file (viewed January 9, 2009). Available via ProQuest Digital Dissertations. Includes bibliographical references (p. 25-26).
5
Huang, Dennis Shihchang. "Immunological changes in retrovirus-infected mice." Diss., The University of Arizona, 1993. http://hdl.handle.net/10150/186463.
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Acquired Immune Deficiency Syndrome (AIDS), a progressive immunodeficiency induced by Human Immunodeficiency Virus (HIV), frequently sets the stage for life-threatening tumors and opportunistic infections. The proposed study focuses on the immunological changes associated with HIV infection. Often superimposed diarrhea, causing malabsorption and malnutrition, leads to further immunosuppression and accelerated deterioration in many patients. The pathomechanism of Cryptosporidium-induced diarrhea is poorly understood and its relation to AIDS urgently requires investigation. We used LP-BM5 murine leukemia virus (MuLV)-infected C57BL/6 mice to model AIDS and thereby study the immunological changes in human retrovirus infection. Production of Th1 cytokines (IL-2 and IFN-γ) was suppressed, whereas Th2 cytokine production (IL-4, IL-5, IL-6, and IL-10) was enhanced in spleen and mesenteric lymph nodes (MLN) during retrovirus infection. However, increased secretion of IFN-γ in the MLN of retrovirus-infected mice may represent incremental production and release by non-Th1 cells. Lymphoid cell population changes in gut-associated lymphoid tissues (GALT) were documented 4 months after retrovirus infection. Total lymphoid cell numbers decreased in Peyer's patches and CD4⁺ cell numbers decreased in the intestinal lamina propria (ILP). Total lymphoid cell numbers increased in MLN but the relative percentages of surface IgA⁺, cytoplasmic IgA⁺ (cIgA⁺), and cIgM⁺ cells were decreased. Cryptosporidium infestation in retrovirus-infected mice decreased following the administration of pooled bovine colostrum containing a high titer of antibody demonstrating the potential efficacy of passive humoral immunity. Changes in the host cellular immune apparatus, following Cryptosporidium infection, were as follows: (1) increased γδ-TCR⁺ cells in the ILP 6 and 10 days post-infection, (2) decreased CD4⁺ cells in the ILP and intraepithelium 10 days post-infection, (3) reduced IgA⁺ and IgG⁺ cells in the ILP 6 and 10 days post-infection, and (4) increased IgE⁺ cells 6 days post-infection. This altered cellular profile indicates the potential for aberrant cytokine production which may be responsible for the compounded immunodeficiency during retrovirus infection. Overall, the findings underscore the importance of understanding both humoral and cell-mediated immunological influences before the rational development of a therapy against opportunistic cryptosporidial infection in AIDS patients can be undertaken.
6
Ou, Linda Ye. "Hyperactive p53 leads to age-related phenotypes in mice model." Diss., [La Jolla, Calif.] : University of California, San Diego, 2009. http://wwwlib.umi.com/cr/ucsd/fullcit?p1460672.
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Dulawa, Stephanie C. "The neural substrates of sensorimotor gating in serotonin receptor mutant mice /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2000. http://wwwlib.umi.com/cr/ucsd/fullcit?p9963658.
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Ralph, Rebecca Jeanette. "Dopamine modulation of prepulse inhibition and locomotor behavior in knockout mice /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2001. http://wwwlib.umi.com/cr/ucsd/fullcit?p3001269.
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Stone, Erica Lyn. "Colitis, hypothyroidism, and immunological alterations in mice deficient in glycan branching enzymes." Diss., [La Jolla, Calif.] : University of California, San Diego, 2009. http://wwwlib.umi.com/cr/ucsd/fullcit?p3344604.
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Thesis (Ph. D.)--University of California, San Diego, 2009.Title from first page of PDF file (viewed March 13, 2009). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references.
10
Christiansen-Weber, Trudy A. "Thymic expression of human wild-type p53 in transgenic mice alters normal thymocyte development and in p53-deficient mice restores radiation-induced apoptosis but fails to prevent thymic lymphoma /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 1998. http://wwwlib.umi.com/cr/ucsd/fullcit?p9904824.
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Hood, Kristin L. "Effects of altered kinase signaling on memory and synapse plasticity in transgenic mice /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2001. http://wwwlib.umi.com/cr/ucsd/fullcit?p3013709.
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12
Rodewald, Tenaya. "Striatal contribution to learning and memory : some findings from studies if transgenic mice /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2003. http://wwwlib.umi.com/cr/ucsd/fullcit?p3099920.
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Chokshi, Sonia K. "The mechanism of the development of hepatic insulin sensitivity in chromogranin a null mice." Diss., [La Jolla] : University of California, San Diego, 2010. http://wwwlib.umi.com/cr/fullcit?p1477892.
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Thesis (M.S.)--University of California, San Diego, 2010.Title from first page of PDF file (viewed July 13, 2010). Available via ProQuest Digital Dissertations. Includes bibliographical references (leaves 24-28).
14
Chiang, Ming-Yi. "Reverse genetic analysis of nuclear receptors, RXR[gamma], RAR[beta] and Tlx in mice /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 1997. http://wwwlib.umi.com/cr/ucsd/fullcit?p9814539.
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Chow, Renee. "Axonal regeneration following complete spinal cord transection in NgR and NgR/Nogo/MAG knockout mice." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2008. http://wwwlib.umi.com/cr/ucsd/fullcit?p1453351.
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Thesis (M.S.)--University of California, San Diego, 2008.Title from first page of PDF file (viewed July 14, 2008). Available via ProQuest Digital Dissertations. Includes bibliographical references (p. 28-30).
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Bejar, Rafael. "Genetic manipulations of synaptic plasticity, learning, and memory : findings from CaMKII and Kv̳4.2 transgenic mice /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2001. http://wwwlib.umi.com/cr/ucsd/fullcit?p3013705.
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Knapp, Amy Elizabeth. "Is myocyte-derived VEGF in adult mice required for normal skeletal muscle structure and function?" Diss., [La Jolla] : University of California, San Diego, 2009. http://wwwlib.umi.com/cr/ucsd/fullcit?p3360169.
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Thesis (Ph. D.)--University of California, San Diego, 2009.Title from first page of PDF file (viewed July 28, 2009). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references.
18
Pak, Winnie. "The role of Islet2 in the laterality and target specification of retinal ganglion cells in mice /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2004. http://wwwlib.umi.com/cr/ucsd/fullcit?p3144312.
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Menon, Vinal. "The contribution of visceral fat to positive insulin signaling in Ames dwarf mice." Master's thesis, University of Central Florida, 2013. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/5818.
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Ames dwarf (df/df) mice are homozygous for a spontaneous mutation in the prop1 gene due to which there is no development of anterior pituitary cells – somatotrophs, lactotrophs and thyrotrophs, leading to a deficiency of growth hormone (GH), prolactin (PRL) and thyrotropin (TSH). They tend to become obese as they age, but still live longer and healthier lives compared to their wild-type littermates, being very insulin sensitive, showing no signs of diabetes and cancer. These mutant mice also have high circulating levels of anti-inflammatory and anti-diabetic adiponectin. Plasma levels of this adipokine usually decrease with an increase in accumulation of visceral fat (VF). We thus believe that VF in df/df mice, developed in the absence of GH signaling, may be functionally different from the same fat depots in normal (N) mice and may be beneficial, rather than detrimental, to the overall health of the animal. We performed surgeries involving removal of VF depots (epididymal and perirenal fat) in both groups of mice and hypothesize that the beneficial effects of visceral fat removal (VFR) will be present exclusively in N mice as VF in df/df mice contributes to enhanced insulin sensitivity by producing decreased levels of pro-inflammatory adipokines like TNF? and IL-6. We found that VFR improved insulin sensitivity only in N mice but not in the df/df mice. This intervention led to an upregulation of certain players of the insulin signaling pathway in the skeletal muscle of N mice only, with no alteration in df/df mice. The subcutaneous fat of df/df mice showed a downregulation of these insulin signaling genes upon VFR. Compared to N mice, epididymal fat of df/df mice (sham-operated) had increased gene expression of some of the players involved in insulin signaling and a decrease in transcript levels of TNFa. Ames dwarf mice had decreased levels of IL-6 protein in EF and in circulation. High circulating levels of adiponectin and decreased levels of IL-6 in circulation could contribute to the high insulin sensitivity observed in the Ames dwarf mice. Understanding the mechanisms responsible for VF having positive effects on insulin signaling in df/df mice would be important for future treatment of obese diabetic patients.M.S.
Masters
Molecular Biology and Microbiology
Medicine
Biotechnology
20
Novak, Susan Marie. "Gastrointestinal cellular and humoral immune responses in BALB/c mice infected with Cryptosporidium parvum." Diss., The University of Arizona, 1991. http://hdl.handle.net/10150/185563.
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Immunohistochemical analysis of intestinal tissue from infected and uninfected neonatal mice was performed to determine immune responsiveness to Cryptosporidium parvum at the gut level. Infected mice showed a significant increase in T cell (T helper/T cytotoxic/suppressor) populations (p < 0.001), macrophages (p < 0.001), IL-2R positive cells (p < 0.001 at 16 days PI), and IgA positive cells (p < 0.001 at 16 days PI) compared to control (uninfected) animals. No differences between the two groups of animals existed for B cell populations of the IgG (p = 0.264) and IgM (p = 0.646) isotype. Cellular immunity seems to be primarily responsible for clearing cryptosporidial infection from infected animals. Humoral immunity mediated by B cells of the IgA isotype could be a secondary (delayed) factor which aids in the recovery of the animal. Neonatal mice were also infected with C. parvum to describe the susceptibility dynamics in this animal model. Percent infectivity of the animals (infected at various days of age beginning on day 4 and ending at day 18) began to decrease at 10 days of age (33% infectivity). Infectivity percentages varied up until 14 days of age and older when all of the animals inoculated were refractory to infection. Why this refractiveness to infection occurs as the animals age is still unknown. In another study neonatal mice infected at 4 days of age continued to be positive for parasites up until 25 days of age (21 days PI). Percent infectivity began to vary at 20 days of age (16 days PI) which meant that only a certain percentage of the mice tested at that time point were positive for C. parvum. Prior to 20 days of age 100% of the animals tested were infected. Proliferative responses of spleen cells from infected and control mice to C. parvum antigen were measured. Spleen cells from infected animals responsed to C. parvum antigen in vitro (stimulation index (SI) = 14.52 (infected mouse #1); 14.23 (infected mouse #2)) whereas cells from uninfected mice did not (SI = 1.12 (control mouse #1); 1.07 (control mouse #2)). The spleen seems to be one organ involved in the immune circuitry responsible for clearance of cryptosporidiosis in neonatal mice.
21
Baharani, Akanksha. "Electroconvulsive shock ameliorates disease processes and extends survival in Huntington mutant mice." Master's thesis, University of Central Florida, 2010. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/4565.
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At present, only symptomatic therapy is available and effective therapeutic approaches to slow the disease process have yet to be developed. Previous studies have shown that electroconvulsive shock (ECS) induces the production of growth factors including BDNF and the molecular chaperones HSP40 and HSP70. Because ECS can stimulate the production of neuroprotective proteins, we determined whether ECS treatment could slow the progressive nature of the disease process and provide a therapeutic benefit in a mouse model of HD. ECS or sham treatment was administered to male N171-82Q Htt mutant mice. End points measured included motor function, striatal and cortical pathology, and levels of neurotrophic factors, protein chaperones, and proteins involved in synaptic plasticity. ECS treatment delayed the onset of motor symptoms, reduced body weight loss and extended the survival of HD mice. Striatal neurodegeneration was attenuated and levels of neurotrophic factors, protein chaperones and mitochondria-stabilizing protein were elevated in striatal cells of ECS-treated compared to sham-treated HD mice. Our findings suggest that ECS can increase the resistance of neurons to mutant huntingtin sic] resulting in improved functional outcome and extended survival. The potential of ECS as a treatment for HD patients merits further consideration.; Huntington's disease (HD) is a devastating autosomal dominantly inherited neurological disorder caused by an abnormal expansion of CAG trinucleotide repeats in the gene coding for the N-terminal region of the huntingtin (Htt) protein, which leads to the formation of a polyglutamine stretch. The greater the CAG repeats, the earlier the onset of the disease. The polyglutamine stretch destabilizes the Htt protein leading to misfolding, abnormal processing, aggregation, and inclusion formation. Mutant Htt protein is believed to damage and kill neurons in the striatum by a mechanism involving increased oxidative and metabolic stress, and impaired adaptive cellular stress responses. A large number of abnormalities have been reported in HD, including transcription deficits, energy impairment, excitotoxicity, and lack of trophic support. Reduced trophic support contributes importantly to striatal degeneration in human HD. Specifically, brain-derived neurotrophic factor (BDNF) expression is reduced in patients with HD. BDNF is also decreased in brain tissue from mice transgenic for mutant Htt. BDNF levels influences the onset and the severity of motor dysfunction in HD mice. In addition to BDNF, levels of the molecular chaperones heat shock proteins (Hsp40 and 70) decrease progressively in HD brain. Hsp70 is a highly stress-inducible member of a chaperone family of proteins that functions to prevent misfolding and aggregation of newly synthesized mutant proteins and stress-denatured proteins. Hsps appear to play a critical role in HD since expression of active heat shock factor HSF1, a transcription factor responsible for the induction of Hsps, markedly reduces polyglutamine aggregate formation in both cell and mouse models. Many efforts have been made to develop preventive treatments for HD because of the strong genetic link and a freely available genetic test to identify individuals at risk.ID: 029050783; System requirements: World Wide Web browser and PDF reader.; Mode of access: World Wide Web.; Thesis (M.S.)--University of Central Florida, 2010.; Includes bibliographical references (p. 53-80).
M.S.
Masters
Burnett School of Biomedical Sciences
Sciences
Biotechnology
22
Rafie, Christopher A. "Statics and dynamics of cerebral blood ilow is mediated through Hypoxia-inducible factor 2-alpha in the tumor suppressor von Hippel-Lindau knock-out mice." Diss., [La Jolla] : University of California, San Diego, 2009. http://wwwlib.umi.com/cr/ucsd/fullcit?p1464663.
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Thesis (M.S.)--University of California, San Diego, 2009.Title from first page of PDF file (viewed June 15, 2009). Available via ProQuest Digital Dissertations. Includes bibliographical references (p. 13-15).
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Shahbazian, Lotfollah Masoud. "Dietary ethanol modulates immune responses, and alter resistance to Streptococcus pneumoniae in LP-BM5 retrovirus infected mice." Diss., The University of Arizona, 1993. http://hdl.handle.net/10150/186594.
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A murine model of acquired immunodeficiency syndrome (AIDS) was developed by infecting C57BL/6 mice with murine leukemia retrovirus LP-BM5. Murine AIDS shares many features with human AIDS. Murine and human AIDS cause impairment of cell-mediated and humoral immune responses, and increase risk of opportunistic infection such as Streptococcus pneumoniae. Cofactors such as ethanol may determine the severity of the retrovirus infection and the rate of progression to AIDS. Changes in nutritional status due to retrovirus infection or ethanol consumption, can play an important role in immunomodulation in the animal. Immunomodulation observed in animals with chronic ethanol ingestion is associated with age of the animal, the nutritional composition of the diet, and the amount of ethanol consumed. Young mice are more sensitive to the immunomodulating effects of ethanol and diet than mature mice. The percentage of B cells in mature mice was significantly increased with consumption of nutritionally superoptimal diet containing ethanol while ethanol ingestion with a nutritionally inadequate diet severely decreased the percentage of B cells when compared to control or pair-feeding. Cytokine secretion, and natural killer cell and phagocytic activities were modulated by ethanol as well as by the nutritional quality of the diet. Both retrovirus infection and ethanol consumption affected survival rate after Streptococcus pneumoniae infection in mice. Chronic ethanol consumption, but not retrovirus infection resulted in significant reduction in serum level of anti pneumococcal polysaccharide antibody which in combination with complement system make up an important part of host defense against S. pneumoniae. However, retrovirus infection significantly reduced resistance to S. pneumoniae. Retrovirus infected mice fed a diet containing a high concentration of ethanol for short term exhibited a greater resistance to S. pneumoniae infection than mice fed diets with low concentration or no ethanol. S. pneumoniae antigen immunization improved survival of the mice infected with S. pneumoniae. In conclusion, ethanol and nutritional adequacy of diet induced immunomodulation of the host. Ethanol consumption during retroviral infection may accelerate the progression of murine AIDS through changes in the lymphoid cells and resistance to S. pneumoniae infection.
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Wang, Yuejian. "Influence of vitamin E supplementation on nutritional status and immune response in ethanol-fed mice and murine AIDS." Diss., The University of Arizona, 1994. http://hdl.handle.net/10150/186670.
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LP-BM5 murine leukemia retrovirus infection in C57BL/6 mice rapidly produces murine AIDS with many functional similarities to human AIDS, including progressive lymphoproliferation and increasing severe immunodeficiency. The present studies indicated that retrovirus infection induces immune dysfunctions via modulating the cytokine production, and affects the thymus, producing altered T cell differentiation via the dysregulation of thymocyte cytokine secretion. In addition, retrovirus infection can directly cause malnutrition, possible via damaging gastrointestinal cells, thereby leading to malabsorption. Such malnutrition has the theoretical potential to accelerate development of AIDS via immunosuppression secondary to nutritional deficiency. Chronic ethanol consumption in the mice altered the cytokine release, and impaired immune response, and disrupted T cell maturation, which increase host susceptibility to infection. Chronic ethanol consumption may be one of the co-factors accelerating development of human AIDS after retrovirus infection. The results from this study suggest that dietary ethanol, upon retrovirus infection or prior to retrovirus infection, aggravates progression of immune dysfunction and affects T cell maturation in the thymus, leading to AIDS as dietary ETOH modifies production of immunological regulatory cytokines by splenocytes and thymocytes. Furthermore, ethanol can directly aggravate undernutrition initiated by retrovirus infection. Such ethanol-induced malnutrition in AIDS may also be a cofactor, accelerating development of AIDS via immunosuppression secondary to nutritional deficiencies. Vitamin E supplementation enhances immune responses. The immunostimulatory nature of vitamin E does provide a basis for its use in the modulation of the various cell components and immune functions, and its consequent therapeutic use during AIDS and alcoholics. The findings in the study clearly demonstrated that dietary vitamin E supplementation can modulate dysregulation of cytokines initiated by dietary EtOH and restore immune dysfunctions induced by EtOH ingestion. The potential therapeutics of vitamin E supplementation for AIDS treatment has also been determined in this study. Vitamin E supplementation, even at extremely high levels, can help to restore levels of tissue nutrients, cytokine dysregulation and some immune dysfunctions initiated by retrovirus infection during murine AIDS. Thus, the vitamin E supplementation may provide additional therapeutic approaches for treatment of HIV infected patients or alcoholics without additional immunotoxicity.
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Darban, Hamid Reza. "Opportunistic infections in mice infected with LP-BM5 murine retrovirus on a binge ethanol diet." Diss., The University of Arizona, 1991. http://hdl.handle.net/10150/185419.
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A murine model of AIDS (Acquired Immune Deficiency Syndrome) for study of immunomodulatory effects of alcohol on opportunistic infection was developed. C57BL-6 female mice were infected with murine retrovirus, LP-BM5. Mice were fed a liquid diet containing alcohol which produced withdrawal upon cessation. Controls were fed the diet with sucrose replacing ethanol. Dramatic differences were observed in spleen weight and thymus weight, but not body weight in virus infected or virus infected mice fed the alcohol diet. Ethanol suppressed the numbers of T-cells and macrophages. There was significant changes due to virus infection with and without alcohol treatment in T-subsets, B-cells and macrophages. However none were seen due to ethanol in uninfected controls. Alcohol further suppressed immune functions in retrovirally infected mice beyond that caused by the virus. Some mice were challenged with Streptococcus pneumoniae and Cryptosporodium. Adult mice that had been infected with LP-BM5 virus for 3, 4, or 5 months, when challenged by the oral route with Cryptosporidium, exhibited significant colonization on the intestinal villiae by this organism 10 days following oral challenge. Control mice did not show any oocyst in the villiae after 10 days following oral challenge. Resistance to S. pneumoniae was significantly reduced by retroviral infection, but not by short-term, binge, exposure to dietary ethanol. After 38 days of LP-BM5 infection, the virus infected alcohol fed group showed the shortest survival. The effects of immunization to S. pneumoniae antigens, as well as adoptively transferred cells in virally infected mice were studied. Survival of the mice to S. pneumoniae were influenced by different immunizations. The virus infected group had a much faster death rate in comparison than longer surviving unifected controls. Immunization played an important role in delaying the death rate in all treated groups. Transferring normal spleen cells from healthy, unimmunized mice also enabled the retrovirally infected mice to survive the bacterial infection longer than unimmunized, but retrovirally infected mice. This indicated the potential to enhance resistance by immunization and the transfer of immunocompetent cells to a system, immunosuppressed by retroviral infection. Clearly, retroviral infection modulates resistance with additional effects of ethanol. This model further expands and defines LP-BM5 infection as a murine model of retrovirally induced immune deficiency.
26
Kalkvik, Haakon Myklevoll. "Conservation and population biology: genetics, demography and habitat requirements of the Atlantic coast beach mice." Doctoral diss., University of Central Florida, 2012. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/5334.
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The conservation biology field seeks to preserve biodiversity and the processes shaping that variation. Conservation biology is intimately tied to evolutionary research, in order to identify evolutionary distinct lineages that may be in danger of disappearing. Interestingly, patterns and processes of lineage divergence and persistence change with respect to spatial and temporal scale. I seek to evaluate biodiversity, the factors that have shaped this heterogeneity, and how this variability persists. To accomplish this I used a phylogeographic approach as well as niche and population modeling on the Peromyscus maniculatus species group found widely distributed in North America. My emphasis was on the southeastern U.S. species P. polionotus and its distinct beach forms. At a continental scale, I found that environmental niches are likely involved in generating and/or maintaining genetic lineages within the P. maniculatus species group. These findings add to a growing number of studies that have identified lineages occupying different environmental spaces. At a regional scale, I supported the hypothesis that barrier islands on the Atlantic coast of Florida were colonized by an ancestral form of P. polionotus by a single colonization, from the central Florida area. Subsequently, at least two distinct lineages diverged (P. p. phasma and P. p. niveiventris). I also found evidence that suggests that the extinct form of beach mouse (P. p. decoloratus) is part of the P. p. phasma lineage. At the population level, I evaluated changes in genetic diversity in historical samples compared to those that experienced recent human encroachment on natural habitat I used tissue preserved in natural history collections to compare with live-trapped specimens, and found that P. p. niveiventris has maintained historical genetic diversity levels. I suggest that the continuation of historical levels of genetic diversity is due to the presence of a single large area of continuous habitat in the central portion of the species' current distribution. Finally, I evaluated the importance of scrub and beach habitat to the population dynamics of beach mice. Beach mice have traditionally have been associated with beach dunes rather than with the scrub habitat found more inland on barrier islands. Using almost three years of capture-recapture data from Cape Canaveral Air Force Station (CCAFS), I created a stochastic matrix model to assess the relative contribution of populations from the two different habitats to a variety of demographic measures. Both field data and model results provided evidence that the population dynamics of beach mice may rely much more on scrub habitat than formerly documented. Overall, my research emphasized a hierarchical approach to evaluate biodiversity and the processes shaping differentiation at different spatial and temporal scales. The methods and findings give insight into speciation at different scales, and can be applied to a wide range of taxa for questions related to evolutionary and conservation biology.ID: 031001408; System requirements: World Wide Web browser and PDF reader.; Mode of access: World Wide Web.; Adviser: Christopher L. Parkinson.; Co-adviser: I. Jack Stout.; Thesis (Ph.D.)--University of Central Florida, 2012.; Includes bibliographical references.
Ph.D.
Doctorate
Biology
Sciences
Conservation Biology; Ecology and Organismal Biology
27
Li, Liang. "Innervation, distribution and morphology of calcitonin gene related peptide and substanceP immunoreactive axons in the whole-mount atria of FVB mice." Master's thesis, University of Central Florida, 2010. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/4598.
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Degeneration of nociceptive afferent axons and terminals in the heart is associated with painless sudden cardiac death. However, innervation, distribution and morphological structures of sympathetic cardiac nociceptive afferent axons and terminals have not yet been fully characterized. The aim of the present study is to characterize the density, arrangement, and structural features of differentiated sympathetic afferent axons and terminals in whole-mount FVB mouse atria. FVB mice (3-6 months old) were perfused and the tissues were fixed. The right and left atria were processed with immunohistochemistry. Calcitonin gene-related peptide (CGRP) and substance P (SP) are two neuropeptides which have been widely used to label sympathetic nociceptive afferent axons in many tissues. CGRP (rabbit anti-CGRP) and SP (Goat anti-SP) primary antibodies were applied, followed by Alexa Fluor 594 and 660 conjugated secondary antibodies. Whole-mount preparations of right and left atria were examined using a laser scanning confocal microscope. We found that 1) CGRP immunoreactive (IR) axon bundles innervated the right and left atria including the auricle and entrance area of the superior vena cava, the inferior vena cava, left precaval vein and pulmonary veins. Large axon bundles entered the area from the major veins and bifurcated into smaller axon bundles and single axon fibers to form terminal end-nets and free endings in the epicardium at each region with a similar pattern. In the atrial muscle layer, varicose CGRP-IR axons had close contacts with muscle fibers. In addition, CGRP-IR axons terminated in the intrinsic cardiac ganglia (ICGs) with varicosities surrounding individual ganglionic principle neurons (PNs). In the aortic arch, the CGRP-IR fibers exhibited similar terminal structures to those seen in the atria. 2) SP-IR axons also projected to the right and left atria and aorta.; Similar to CGRP-IR axons, these SP-IR axons also formed end-nets and free endings in these areas. In cardiac ganglia, SP-IR axons formed varicose endings around many individual PNs. However, a salient difference was found: There appeared to be fewer SP-IR axons and terminals than CGRP-IR axons and terminals in the atria. 3) None of the cardiac PNs in ICG were CGRP-IR or SP-IR. 4) Many SP-IR axon terminals around PNs within ICGs and atrial muscles were found to have colocalized expression of CGRP-IR. Collectively, our data for the first time documented the distribution patterns and morphology of sympathetic afferent axons and terminals in each region of the atria in the mouse model. This will provide a foundation for future analysis of the pathological changes of sympathetic afferent nerves in the atria in different disease models (e.g., diabetes, sleep apnea, and aging). This study was supported by NIH R01 HL-79636.ID: 030423285; System requirements: World Wide Web browser and PDF reader.; Mode of access: World Wide Web.; Thesis (M.S.)--University of Central Florida, 2010.; Includes bibliographical references (p. 42-48).
M.S.
Masters
Department of Molecular Biology and Microbiology
Medicine
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Feltquate, David Marc. "Helper T Cell Differentiation in DNA-Immunized Mice: A Dissertation." eScholarship@UMMS, 1998. http://escholarship.umassmed.edu/gsbs_diss/181.
Full textAbstract:
DNA immunization, inoculation with an antigen-expressing plasmid DNA, is a new method for generating an antigen-specific immune response. At the time these investigations began, very little was known about the immune response produced by DNA vaccines. Thus, the first aim of our studies was to perform a detailed examination of the antibody response generated by DNA immunization with an influenza hemagglutinin (HA)-expressing DNA in BALB/c mice. Using several different routes and methods of DNA immunization, we observed a number of findings. Although all three forms of DNA immunization elicited strong anti-HA antibody responses, i.m. and i.d. saline DNA immunization required approximately 100 times more DNA than a gene gun DNA immunization to raise an equivalent titer of anti-HA antibody. Indeed, as little as one inoculation and one boost by gene gun of 0.0004 μg of DNA produced a measurable antibody response in 50% of mice. Unexpectedly, we found the isotype of the antibody response differed among groups of mice immunized by different forms of DNA immunization. Intramuscular and i.d. saline DNA immunization produced predominantly an IgG2a anti-HA antibody response, whereas gene gun DNA immunization elicited mostly an IgG1 anti-HA antibody response.
Considering that IgG2a and IgG1 antibody isotypes were known to correlate with Th1 and Th2 immune responses, respectively, we analyzed the type of immune responses produced by i.m., i.d., and gene gun DNA immunization. We found that i.m. and i.d. saline DNA immunization produced a Th1 predominant cellular immune response. In contrast, gene gun DNA immunization produced a Th2 cellular immune response. The differences in the type of immune responses were found to be due to the method of DNA immunization, and not due to the route of DNA inoculation. A gene gun DNA immunization of muscle produced the same IgG1, Th2 immune response as a gene gun DNA immunization of skin, while a saline DNA immunization of muscle and skin produced mostly an IgG2a, Th1 immune response. Each method of DNA immunization created good memory Th cell responses. The type of immune response created by an initial DNA immunization remained fixed even after multiple boosts with the identical method of DNA immunization, following a boost with the alternative method of DNA immunization, or after a viral challenge.
The differentiation of naive Th cells into Th1 or Th2 cells depends on a variety of factors. We performed many experiments to elucidate which factors played a role in the generation of Th1 or Th2 immune responses following saline DNA immunization and gene gun DNA immunization. DNA dose response studies revealed the use of different doses of DNA between groups of saline DNA and gene gun DNA immunized mice did not account for the differentiation of distinct Th cell subsets. Cytokine production inducible by a number of factors inherently associated with either saline DNA or gene gun DNA immunization did not affect Th differentiation. For instance, contamination of plasmid DNA with lipopolysaccharide did not account for differences in the immune response. Immunostimulatory CpG sequences did not affect Th differentiation following DNA immunization, but they did enhance the IgG2a antibody response to coinoculated HA protein. Finally, cotransfection of IFNγ or IL-4 expressing plasmids with an HA-expressing plasmid by gene gun inoculation or as a saline DNA injection did not shift the type of immune response in a Th1 or Th2 direction, respectively. Thus, it appeared that increased cytokine stimulation was not responsible for selective Th subset differentiation.
One factor related to the method of DNA immunization did seem to correlate with Th1 differentiation. Deposition of plasmid DNA extracellulary by saline DNA injections (as opposed to intracellular DNA delivery by gene gun) may have stimulated Th1 immune responses. Manipulating a gene gun DNA immunization to deliver DNA to the dermis (and thus extracellularly) shifted the immune response from that of a Th2 type to a mixed Th1/Th2 type. Furthermore, evidence was gathered demonstrating that pDNA can interact with cell surface molecules and that specific sequences in pDNA can act as a ligand and bind to molecules. Taken together, our data led us to propose a new model for Th1 differentiation following saline DNA immunization. We believe extracellular pDNA binds to an APC cell surface molecule which activates the cell. The activated APC preferentially stimulates naive Th cells to differentiate into Th1 cells.
Finally, studies using a variety of mice differing in their genetic backgound and MHC genotype demonstrated the generality of our findings regarding i.m. saline DNA inoculations of an HA-expressing pDNA. Saline DNA immunization produced IgG2a, Th1-predominant immune responses independent of the genetic background and MHC genotype of the mice. In contrast, the type of immune response elicited by a gene gun DNA immunization was dependent on the MHC genotype of mice. Thus the type of immune response produced by gene gun DNA immunization probably depends on the specific antigen (and its effect on MHC-peptide/TcR interaction and signaling) and is less likely due to any inherent feature associated with the process of gene gun DNA delivery.
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Wagar, Eric James. "Human Lymphocyte Engraftment and Function in HU-PBL-SCID Mice: a Dissertation." eScholarship@UMMS, 2000. http://escholarship.umassmed.edu/gsbs_diss/286.
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The immune system is responsible for defending a host animal from a wide variety of threats. Manipulation of the immune system can result in beneficial outcomes such as immunity to pathogens, or deleterious outcomes such as autoimmunity. Advances in our understanding of how the immune system develops and functions have benefited greatly from studies in animals, particularly in mice where the genetics are well known and a multitude of reagents are readily available for experimental use. Although much has been learned from animal experimentation, it must be cautioned that animals are not humans. Unforeseen outcomes and complications often arise when translating research obtained in animal models to treatment of human patients. A small animal model in which the human immune system can be established and manipulated experimentally in vivo would be valuable for the study of human immune responses in infectious diseases, transplantation, and autoimmunity, and ultimately for translation of these findings to the human patient. Contribution to this model is the overall goal of this thesis.
The severe combined immunodeficiency (Prkdcscid, termed scid) mutation was discovered in 1983 in the C.B-17 strain of mice. Scid mice lack functional T and B lymphocytes and are unable to mount immune responses or reject allogeneic or xenogeneIc grafts. However, C.B-17-scid mice do develop normal or even elevated innate immune function. Based on the ability of scid mice to accept xenografts, human peripheral blood mononuclear cells have been injected to generate "Hu-PBL-scid mice." These Hu-PBL-scid mice have been proposed as an in vivo model of the human immune system. Although this model was described over 12 years ago, there are a number of obstacles that impede its ability to recapitulate human immunity. The Hu-PBL-scid mouse model established using C.B-17-scid mice as recipients is hindered by 1) low levels of human leukocyte engraftment, 2) engraftment of predominately memory/activated human T cells with specificity directed against host murine MHC antigens, 3) rapid transition of engrafted human lymphocytes to a functionally anergic state, and 4) a paucity of knowledge providing an understanding of the mechanisms that underlie engraftment and function of the human lymphocytes in the immunodeficient hosts.
This thesis was initiated at the time the NOD-scid mouse became available for establishment of Hu-PBL-scid mice, and this model has subsequently been termed "Hu-PBL-NOD-scid." The NOD-scid mouse was designed as an improved recipient for human PBL based on its innate immune characteristics. Defects in innate immunity in wild-type NOD/Lt mice include reduced NK cell activity, defects in macrophage development and function, and a lack of hemolytic complement. NOD-scid mice retained these characteristics, and engraft human cells at higher levels compared to C.B-17-scid mice. However, the ratio of CD4+ to CD8+ T cells in Hu-PBL-NOD-scid mice remained skewed towards the CD8+ population, similar to that of the Hu-PBL-C.B-17-scid mouse.
My thesis was based on the overall hypothesis that additional genetic manipulation of the recipient strain would enhance further the engraftment and function of human cells. Based on the engraftment results obtained in NOD-scid mice, we performed these genetic manipulations using the NOD-scid strain as the reference. We first hypothesized that removal of MHC expression would lower human anti-mouse xenoreactivity and enhance engraftment of naïve T cells, a cell population not readily detectable in Hu-PBL-C.B-17-scid or Hu-PBL-NOD-scid mice. Towards this goal, the NOD-scid mouse expressing a targeted mutation for beta-2 microglobulin (B2mnull) mouse was created by Dr. Leonard Shultz at the Jackson Laboratory. Because B2m is required for expression of MHC class I and for development of functional NK cells, we predicted that NOD-scid-B2mnull mice would first exhibit a normalized CD4:CD8 T cell ratio resulting from reduced CD8 engraftment due to decreased human anti-mouse MHC class I reactivity. Since MHC class I molecule expression is required for the development of NK cells, we further predicted that there would be a reduction of NK cell activity, permitting enhanced engraftment. Data presented in this thesis demonstrates that human PBL engraft in NOD-scid-B2mnull mice at levels higher than NOD-scid mice, and with an increased CD4:CD8 T cell ratio. The mechanism(s) responsible for the increased engraftment of human cells in these mice became a major focus of this thesis.
This thesis is composed of three Specific Aims. Specific Aim 1 was to determine the mechanism(s) underlying human cell engraftment and function in Hu-PBL-scid mice. These data are contained in Part 1 of the Results. Specific Aim 2 was to elucidate the costimulation interactions between human T cells and murine host APCs that control the level of engraftment and activation state of the human lymphocytes. These data are contained in Part 2 of the Results. Specific Aim 3 was to utilize these fundamental observations to initiate studies into the induction of primary human immune responses in Hu-PBL-scid mice. Although the goal of these latter studies was not attained, the data from the experiments performed is provided in Part 3 of the Results, and is discussed relative to future directions for this arm of the project.
In Part 1 of the Results, we utilized in vitro and in vivo techniques to study the underlying mechanisms regulating human cell engraftment and function in scid mice. We observed that the absence of mouse MHC class I antigens in NOD-scid-B2mnull mice does not reduce the stimulatory capacity of APCs toward human T cells in vitro. We further demonstrated that naïve human T cells persist for at least 2 weeks in the peritoneal cavity of Hu-PBL-NOD-scid and Hu-PBL-NOD-scid-B2mnull mice. However, in both strains of recipients, the human cells progress to an anergic phenotype as documented by cell surface molecule expression and by functional activity. We further documented that the increased engraftment of human CD4+ T cells observed in NOD-scid-B2mnull mice is due predominantly to the ablation of host NK cell activity. Increased engraftment of human CD4+ cells in NOD-scid-B2mnull mice can be recapitulated in NOD-scid mice by antibody-mediated depletion of residual host NK cells. Finally, we demonstrated that expression of MHC class II molecules by recipient mice facilitated stimulation and engraftment of human cells. However, mouse MHC class II expression is not required for human cell engraftment into scid mice.
In Part 2 of the Results, we addressed the cellular and costimulatory interactions of engrafted human cells in scid mice. Costimulatory interactions between T cells and APC are now known to be critical for the proper activation and functioning of cells in the immune system. Understanding the role of costimulatory interactions between human T cells, human APCs, and mouse APCs became a major focus of this thesis.
We demonstrated that human CD4+ T cells are required for the engraftment of human CD8+ T cells. The mechanism by which human CD4+ cells mediate this "helper" activity requires expression of CD154. Antibody-mediated blockade of CD154 in vivo abrogates human cell engraftment in scid mice. The role of host APCs in the engraftment of human lymphocytes was demonstrated by blocking host CD40 with antibody. Preventing human T cell CD154 interaction with host CD40 on murine APCs blocked human cell engraftment in scid mice, demonstrating the importance of "trans-costimulation" in human T cell activation. This "trans-costimulation" appeared to be mediated by B7 expression on mouse APCs. We further demonstrated that in vivo depletion of human CD8+ T cells in Hu-PBL-NOD-scid mice leads to increased levels of human CD4+ T cells, elevated human immunoglobulin in the serum, and increased incidence of EBV-related lymphoproliferative disorders. These observations suggested that human CD8+ T cells are able to regulate human CD4+ T cell help and provide "surveillance" activity for EBV-related lymphoproliferative disorders.
In Part 3 of the Results, we used the Hu-PBL-scid mouse to initiate experiments designed to generate primary human immune responses in vivo. These experiments were based on our observation that few if any human APCs survive in scid mice, and on reports that dendritic cells (DC) are required for activation of naïve T cells and initiation of a primary immune response. We used recombinant viruses expressing HIV-1 proteins that are being developed as potential vaccines for HIV as our immunizing reagent. For APCs, we used DCs from NOD-scid mice expressing human MHC class II molecules as the source of APCs presenting antigen to the engrafted human T cells in the scid mice. Our attempts to induce a primary immune response using DC from human MHC-transgenic NOD-scid mice were unsuccessful, as were direct immunization protocols. The results section, however, does highlight deficiencies that could be approached experimentally in future studies.
In summary, the results presented in this thesis advance our understanding of the fundamental mechanisms controlling human cell engraftment in scid mice. This information supports the long-term goal of establishing a functional human immune system in a small animal model. We have identified many of the cell interactions and factors that regulate human cell engraftment and function in scid mice, and we have provided insights into host characteristics that will provide optimized engraftment of naïve human T cells. The studies led to the novel observations of the regulation of human CD4+ T cells by human CD8+ T cells, B cell activation, and progression of latent EBV infection to lymphoproliferative disorders in vivo. These studies further provide new information regarding "trans-costimulation", a previously unrecognized mechanism of T cell activation. These results provide data on the fundamental mechanisms that underlie obstacles to the goal of achieving engraftment of a functional human immune system in scid mice.
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Shen, Jun. "Factors influencing topotecan CNS penetration in mouse models." View the abstract Download the full-text PDF version, 2008. http://etd.utmem.edu/ABSTRACTS/2008-026-Shen-Index.html.
Full textAbstract:
Thesis (Ph.D.)--University of Tennessee Health Science Center, 2008.Title from title page screen (viewed on Sept. 17, 2008). Research advisor: Clinton Stewart, Pharm.D. Document formatted into pages (xiii, 105 p. : ill.). Vita. Abstract. Includes bibliographical references (p. 80-102).
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Zhang, Baochun. "NF-KB2 is an autoimmunity regulator and its mutation leads to lymphomagenesis in mice." Connect to full-text via OhioLINK ETD Center, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=mco1145289004.
Full textAbstract:
Thesis (Ph.D.)--Medical University of Ohio, 2006."In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Medical Sciences." Major advisor: Han-Fei Ding. Includes abstract. Document formatted into pages: iv, 163 p. Title from title page of PDF document. Title at ETD Web site: NF-KappaB2 is an autoimmunity regulator and its mutation leads to lymphomagenesis in mice. Bibliography: pages 67-77,106-112,134-161.
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Walker, Christopher J. "The Role of Neurotensin Receptors on Visceral Pain and Activity Levels in Mice." UNF Digital Commons, 2015. http://digitalcommons.unf.edu/etd/588.
Full textAbstract:
This study examines the effects of neurotensin (NT) receptor sites on the sensation of visceral pain. Previous work by researchers has found, through the use of NT analogs, that visceral pain is closely associated with NT receptor 2 (NTSR2). This study tested 70 genetically modified mice. The mice were either missing NTSR1, NTSR2, or were wild-type (WT) mice that were not missing any NT receptors. The mice were injected intraperitoneally with either saline or acetic acid then observed for a 60 minute period and writhing behavior was recorded. Twenty four hours later activity levels were recorded in the open field assay. We found that contrary to previous research, NTSR2 is not solely responsible in the sensation of visceral pain. We also found that NTSR1 plays a more significant role than NTSR2, contrary to previous research. Additionally, we found that the NT receptors may be affected by age related factors. The findings of this study suggest that NTSR2 does in fact play a role in the sensation of visceral pain but that NTSR1 may modulate the degree of activation of NTSR2. It can also be concluded that age may have a role in the effectiveness of NTSR sites in visceral pain. This information allows for further research to analyze possible age-dependent effects of NT receptor sites that could alter the possible usefulness of NT analogues in the future.
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Wiese, Michelle Kim. "Immune stimulation with short-term exposure to extremely low frequency electromagnetic fields in mice (Mus. musculus)." Thesis, Bloemfontein : Central University of Technology, Free State, 2013. http://hdl.handle.net/11462/209.
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Thesis (M. Tech. (Biomedical Technology)) -- Central University of technology, Free State, 2013Electromagnetic fields are present wherever electricity is created. The frequency range of these electromagnetic fields is from extremely low to extremely high. The fields present in domestic areas fall within the extremely low frequency range. These fields are created by domestic electrical appliances and telecommunication. There has been much debate on the effect of exposure to these fields on human health. Research has not yet been able to prove adverse effect of these fields on human health. In fact, the benefits of magneto therapy has been recognized and used for several decades. Recently a specific electromagnetic signal has been under investigation for its ability to stimulate the immune response. This signal is produced by a patented generator, called Immunent Activator. Studies performed with the Immunent Activator signal on farm animals revealed increased feed conversion and decreased intestinal lesions of animals with intestinal infections. Most of the research was performed on fish and fowls and evidence of similar findings in mammals is lacking. In the current study, mice were exposed to the Immunent BV signal for seven days, after which immune cell counts were performed and compared to the immune cell counts of a control group of mice which received no electromagnetic exposure. It was found that the T-lymphocyte population of immune cells in the exposed group of mice was statistically significantly higher than that of the control group. The neutrophil count was statistically significantly lower in the exposed group compared to the control group. These findings revealed evidence of immune stimulation in the mice which were exposed to the Immunent Activator signal. Suggestions for further research could be made with regard to specific mechanisms of immune stimulation. The findings of this and other related studies hold benefits for the farming and health industry.
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Do, Andrew. "The Effects of Growth Hormone and Thyroxine Treatment on the Insulin Signaling of Female Ames Dwarf Mouse Skeletal Muscle Tissue." Honors in the Major Thesis, University of Central Florida, 2013. http://digital.library.ucf.edu/cdm/ref/collection/ETH/id/941.
Full textAbstract:
Ames dwarf (df/df) mice are deficient in anterior pituitary hormones: growth hormone (GH), thyroid stimulating hormone (TSH), and prolactin (PRL) due to a spontaneous, homozygous mutation of prop1[superscript df] gene. These dwarf mice exhibit characteristics such as delayed growth and development coupled with delayed aging, increased lifespan, overall increased insulin sensitivity, as well as resistance to certain diseases and cancers. The mutant mice possess low blood glucose, low serum insulin, and lower body temperature. Their enhanced longevity (about 40-60% longer lifespan than normal mice) is associated with their GH deficiency and disruption in the somatotropic axis (GH/IGF-1 hormonal pathway) as well as increased insulin sensitivity, which is supported by other mutant mouse models for longevity like Snell dwarfs and growth hormone receptor knock-out (GHRKO) mice. When young male Ames dwarf mice were treated with GH replacement therapy, they showed increased body growth to nearly match the normal mouse phenotype. In conjunction to an increase in physical growth, however, GH treatment also decreases the longevity and insulin sensitivity that are characteristic of these mice to levels seen in normal mice. Because of the lack of TSH, they also have undetectable levels of Thyroxine (T4). While T4 treatment didn't increase bodyweight of dwarfs to the same extent as GH treatment, the T4 treated mice retained their enhanced lifespan. Although df/df mice have enhanced whole-body insulin sensitivity, the male skeletal muscle was previously shown to be less responsive to insulin than their liver. In our study we analyzed the insulin signaling pathway in skeletal muscle from female mice after treatment with GH or GH combined with T4. Gene expression and protein expression were investigated in the skeletal muscle of female Ames dwarf mice that were treated with GH or GH and T4 therapy. Real Time Polymerase Chain Reaction (RT-PCR) was used to analyze the expression of mRNA involved with insulin and GH signaling, while western blots were used to analyze protein expression. This project found that female Ames skeletal muscle didn't respond to GH treatment to the same extent as males, and that GH and T4 treatment tends to neutralize the effects seen in GH-only treatment.B.S.
Bachelors
Burnett School of Biomedical Sciences
Molecular Biology and Microbiology
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Lamperti, Edward D. "Characterization of the Gene and Messages for Vasoactive Intestinal Polypeptide in Rat and Mouse: a Thesis." eScholarship@UMMS, 1989. http://escholarship.umassmed.edu/gsbs_diss/233.
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The organization and transcription of the gene for vasoactive intestinal polypeptide (VIP) in rats and mice was investigated using northern- and Southern-blot hybridizations, selective genomic cloning, Sl-nuclease protection assays, oligonucleotide-directed RNase H digestions, and genomic cloning by standard methods. The center of the rat VIP gene and the entire mouse gene were cloned and sequenced. Selective genomic cloning was used to isolate a strongly-hybridizing fragment of the rat VIP gene identified in Southern-blot hybridizations with an existing human VIP cDNA. This fragment contains separate exons encoding VIP and a closely related neuropeptide, peptide histidine-isoleucine (PHI-27). This organization is the same in the mouse gene, which bears a total of seven exons and a close similarity to the human gene for VIP. Although the arrangement of exons suggested that VIP transcripts could be subjected to differential splicing to alter the coding capacity of the final messages, no evidence was found for this possibility. Two bands were seen in northern-blot hybridizations, but exon-specific probes and Sl-protection experiments provided evidence that they differed not in their coding regions but in the extent of their 3'-untranslated ends. RNase H digestions targeted to specific portions of transcripts from the VIP gene were used to resolve the principal band, to demonstrate that it represented a single species of message with sequence from both the VIP and PHI exons.
In the course of the characterization of the murine VIP gene, a new method was developed for generating subclones for DNA sequencing in M13 bacteriophage. The central feature of the partial deletion subcloning method is its employment of frequent-cutting restriction endonucleases to detach different extents of the insert from a construction. The viral construct is first linearized at a unique site between the insert and the site for hybridization of the M13 sequencing primer. The linearized construct is then subjected to partial digestion with different frequent-cutting restriction enzymes. Partially digested products are repaired and religated. Products with deletions from the insert now have the sequencing priming site religated to a portion of the insert that formerly had been distant. Most of the products with deletions in the viral genome are not viable and do not survive the procedure. Subclones are sorted from the pool of transfected products by sizing of single-stranded viral DNA by agarose gel electrophoresis. Selected subclones are subjected to a simple test for the presence of the sequencing priming site. With this method and its associated tests, a variety of restriction enzymes can be used to generate a spectrum of deletion subclones for sequencing. In a simple trial of this method with an unknown 3.3 kilobasepair cDNA, a set of subclones was generated to allow sequencing to span the cDNA in one direction.
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Jarvis, Christopher D. "Mouse Antibody Response to Group A Streptococcal Carbohydrate: A Thesis." eScholarship@UMMS, 1989. https://escholarship.umassmed.edu/gsbs_diss/227.
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In an attempt to more fully understand the generation of antibody diversity to carbohydrate antigens, we produced and characterized a panel of hybridoma cell lines specific for group A streptococcal carbohydrate from mice injected with the intact bacteria (minus the hyaluronic acid capsule and cell wall protein antigens). We have analyzed the use of heavy and light chain variable region genes in the early (day 7) and late response (hyperimmune) and have determined the nucleotide sequence of the dominant VH gene used in several of our hybridomas. Our data allowed us to assess the extent to which the recombination of various V, D, and J gene segments and somatic mutation contribute to antibody diversification in this system. In this report we confirm that a minimum of two VH and four VK gene segments are used to encode this response. We extend this analysis to show that multiple D and J gene segments are used and that a significant amount of junctional variability is tolerated in CDR 3. Our results also suggest that there is a positive selection for somatic mutation in CDR 1 during the hyperimmune response to group A streptococcal carbohydrate.
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Herr, Roger Alan. "Evaluation of Coccidioides posadasii antigens as recombinantly expressed monovalent, divalent, and chimeric vaccine candidates." Connect to full-text via OhioLINK ETD Center, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=mco1160404292.
Full textAbstract:
Thesis (Ph.D.)--Medical University of Ohio, 2006."In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Medical Sciences." Major advisor: Garry Cole. Includes abstract. Document formatted into pages: ii, 206 p. Title from title page of PDF document. Title at ETD Web site: Evaluation of two homologous Coccidioides posadasii antigens as recombinantly expressed monovalent, divalent, and chimeric vaccine candidates. Bibliography: pages 75-83, 116-120, 165-169, 185-204.
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Tanner, Lisa. "Effects of early acoustic stimulation of prepulse inhibition in mice [electronic resource] / by Lisa Tanner." University of South Florida, 2003. http://purl.fcla.edu/fcla/etd/SFE0000070.
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Professional research project (Au.D.)--University of South Florida, 2003.Title from PDF of title page.
Document formatted into pages; contains 20 pages.
Includes bibliographical references.
Text (Electronic thesis) in PDF format.
ABSTRACT: The purpose of this study was to determine the effects of an atypical pattern of early acoustic stimulation on auditory development. Previous human research suggests that the acoustic environment of pre-term human infants in the Neonatal Intensive Care Unit (NICU) negatively affects some aspects of auditory development. Animal research suggests that premature auditory stimulation interrupts auditory development. Because mice are born before their auditory systems are developed, they make an excellent model for research on fetal and postnatal plasticity of the auditory system. The premature auditory state of newborn mice is similar to that of the NICU pre-term infant, albeit, natural for mice C57 mouse pups were exposed to an augmented acoustic environment (AAE) of a nightly 12-hour regiment of 70 dB SPL noise burst, beginning before age 12 days (onset of hearing) and lasting for one month.
ABSTRACT: The prepulse inhibition (PPI) of mice exposed to the AAE was compared to that of non-exposed mice to observe short-term and long-term effects. Results showed that the prepulse inhibition of the AAE exposed mice did not differ significantly from that of the non-exposed mice. However, it is possible that the measurement used, PPI, may not have been appropriate or that the AAE may not have been an appropriate simulation of the NICU environment.
System requirements: World Wide Web browser and PDF reader.
Mode of access: World Wide Web.
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Baker, Mike, and University of Lethbridge Faculty of Arts and Science. "Role of epigenetic changes in direct and indirect radiation effects." Thesis, Lethbridge, Alta. : University of Lethbridge, Faculty of Arts and Science, 2008, 2008. http://hdl.handle.net/10133/650.
Full textAbstract:
For over 100 years, cancer radiation therapy has provided patients with increased
survival rates. Despite this success, radiation exposure poses a threat to the progeny of
exposed parents. It causes transgenerational genome instability that is linked to
transgenerational carcinogenesis. The exact mechanisms in which this instability occurs
have yet to be discovered. Current evidence points to their epigenetic nature, specifically
changes in DNA methylation.
Using mouse and rat models, this thesis investigated the transgenerational effects
of radiation in the offspring from parents who received whole body or localized exposure
to ionizing radiation (IR). Both types of exposure resulted in significant global DNA
hypomethylation in the somatic tissues of the progeny. These changes were paralleled by
the significantly decreased levels of methyltransferases and methyl-CpG-binding protein.
In summary, our results suggest that both localized and whole body parental
exposures to IR result in transgenerational epigenetic instability within the unexposed
offspring.vii, 106 leaves : ill. ; 29 cm.
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Oktay, Yavuz. "Defining a novel role for hypoxia inducible factor-2 alpha (HIF-2a)/EPAS1 : maintenance of mitochondrial and redox homeostasis." Access to abstract only; dissertation is embargoed until after 12/20/2006, 2005. http://www4.utsouthwestern.edu/library/ETD/etdDetails.cfm?etdID=134.
Full text
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Steinman, Heather Anne. "Mdm2 and Mdm4 Functions in Growth Control: a Dissertation." eScholarship@UMMS, 2004. http://escholarship.umassmed.edu/gsbs_diss/306.
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Amplification and/or overexpression of the Mdm2 oncogene occurs in many human cancers. Mdm2 promotes cellular proliferation, interferes with apoptosis, and induces tumor formation through the negative regulation of the p53 tumor suppressor. More than thirty percent of human tumors overexpressing Mdm2 also present with alternatively spliced Mdm2 isoforms that cannot directly bind p53. The presence of Mdm2 isoforms in tumors correlates with a higher tumor grade and a poorer prognosis for the patient. To investigate the function of Mdm2 isoforms in tumorigenesis, we have isolated a number of Mdm2 splice forms from tumors obtained from Mdm2-transgenic mice and find that the most frequently observed splice form in human tumors, Mdm2-b, is conserved in mice. Although the Mdm2-b protein is incapable of binding to p53 and is unable to localize to the nucleus, we demonstrate that Mdm2-b promotes cell growth in NIH3T3 cells, Rb-deficient, p19-deficient, and p53-deficient primary cells. We also show that Mdm2-b inhibits apoptosis in response to serum withdrawal and restimulation, doxorubicin treatment, and TNF-alpha administration. Mdm2-b induces foci formation in vitro and directly contributes to tumor formation in GFAP-Mdm2 transgenic mice. We propose that Mdm2-b promotes tumor growth by upregulating RelA (P65) protein levels and activity in a p53-independent manner. To better understand additional functions of Mdm2 that are p53-dependent, we have generated an Mdm2 conditional mouse model. Using primary mouse embryonic fibroblasts derived from Mdm2 conditional mice, we demonstrate that p21 is required for p53-dependent apoptosis initiated by Mdm2 loss. In support of this observation, we also note that p21-loss partially rescues embryonic lethality of Mdm2 null mice. We further show that p21-loss partially rescues the embryonic lethality caused by the loss of the Mdm2 family member, Mdm4. We address the possibility that Mdm2 and Mdm4 may play redundant roles during embryonic development and find that Mdm2 overexpression fully rescues the embryonic lethality resulting from Mdm4 loss. Our findings demonstrate that both Mdm2 and Mdm4 play critical roles in modulation of the p53 tumor suppressor pathway and that their deregulation can result in tumor formation through both p53-dependent and independent pathways.
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O'steen, Jennifer Robin. "Prepulse Inhibition and the Acoustic Startle Response in Nine Inbred Mouse Strains." Scholar Commons, 2003. https://scholarcommons.usf.edu/etd/1443.
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This study examined the effects of genetic background on the acoustic startle response (ASR) and its modulation by prepulse inhibition (PPI) by comparing nine inbred strains of mice. The ASR, a jerk-like motor reflex, is elicited by bursts of noise or tones with sound pressure levels of 80-90 dB and greater. PPI is a type of modulation of the ASR, requires no training, and results in observable response in both mice and humans.
Data were obtained from nine inbred mouse strains, sixteen per strain, which were shipped at approximately 3-5 weeks old from The Jackson Laboratory. In general, ASRs were generally smaller when the startle stimulus was less intense. PPI was relatively weak for the 4 kHz prepulse, and stronger with prepulses of 12 kHz and 20 kHz. However, means varied widely across strains for both ASR and PPI, suggesting a strong influence of genetic background on these behaviors. In addition to genetic influences, peripheral hearing loss and central auditory processing factors must be taken into consideration.
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Walz, Paul S. "Influence of pathogenic bacterial determinants on genome stability of exposed intestinal cells and of distal liver and spleen cells." Thesis, Lethbridge, Alta. : University of Lethbridge, Dept. of Biology, c2011, 2011. http://hdl.handle.net/10133/3405.
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Most bacterial infections can be correlated to contamination of consumables such as food and water. Upon contamination, boil water advisories have been ordered to ensure water is safe to consume, despite the evidence that heat-killed bacteria can induce genomic instability of exposed (intestine) and distal cells (liver and spleen). We hypothesize that exposure to components of heat-killed Escherichia coli O157:H7 will induce genomic instability within animal cells directly and indirectly exposed to these determinants. Mice were exposed to various components of dead bacteria such as DNA, RNA, protein or LPS as well as to whole heat-killed bacteria via drinking water. Here, we report that exposure to whole heat-killed bacteria and LPS resulted in significant alterations in the steady state RNA levels and in the levels of proteins involved in proliferation, DNA repair and DNA methylation. Exposure to whole heat-killed bacteria and their LPS components also leads to increased levels of DNA damage.xiv, 132 leaves : ill. (chiefly col.) ; 29 cm
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Merrifield, Matthew, and University of Lethbridge Faculty of Arts and Science. "Radiation-induced deregulation of PiRNA pathway proteins : a possible molecular mechanism underlying transgenerational epigenomic instability." Thesis, Lethbridge, Alta. : University of Lethbridge, Dept. of Biological Science, c2011, 2011. http://hdl.handle.net/10133/2617.
Full textAbstract:
PiRNAs and their Piwi family protein partners are part of a germline specific epigenetic regulatory mechanism essential for proper spermatogenesis, silencing of transposable elements, and maintaining germline genome integrity, yet their role in the response of the male germline to genotoxic stress is unknown.
Ionizing radiation (IR) is known to cause transgenerational genome instability that is linked to carcinogenesis. Although the molecular etiology of IR-induced transgenerational genomic instability is not fully understood, it is believed to be an epigenetically mediated phenomenon. IR-induced alterations in the expression pattern of key regulatory proteins involved in the piRNA pathway essential for paternal germline genome stability may be directly involved in producing epigenetic alterations that can impact future generations.
Here we show whole body and localized X-irradiation leads to significant altered expression of proteins that are necessary for, and intimately involved in, the proper functioning of the germline specific piRNA pathway in mice and rats. In addition we found that IR-induced alterations to piRNA pathway protein levels were time and dose dependent.ix, 123 leaves : ill. (some col.) ; 29 cm
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Li, Hongmei. "Studying physiological functions of APP using mice models." 2008. http://www4.utsouthwestern.edu/library/ETD/etdDetails.cfm?etdID=405.
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Denton, Wesley Paul. "Mucosal HIV-1 Transmisson in Humanized Mice." 2008. http://www4.utsouthwestern.edu/library/ETD/etdDetails.cfm?etdID=364.
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Myers, Kalisa Galina. "UCHLI in the mammalian nervous system." 2008. http://www4.utsouthwestern.edu/library/ETD/etdDetails.cfm?etdID=408.
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Myers, Kalisa Galina. "UCHL1 in the mammalian nervous system." 2008. http://www4.utsouthwestern.edu/library/ETD/etdDetails.cfm?etdID=408.
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Suh, Jae Myoung. "From Flies to Mice: Drosophila as a Model System to Study Fat Biology." 2006. http://www4.utsouthwestern.edu/library/ETD/etdDetails.cfm?etdID=230.
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Su, Jie. "Origin and function of CD8 T cells in MHC class Ia-deficient mice." 2005. http://edissertations.library.swmed.edu/pdf/SuJ122005/SuJie.pdf.
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