Matching Items (235)
Description
Vertebrate genomes demonstrate a remarkable range of sizes from 0.3 to 133 gigabase pairs. The proliferation of repeat elements are a major genomic expansion. In particular, long interspersed nuclear elements (LINES) are autonomous retrotransposons that have the ability to "cut and paste" themselves into a host genome through a mechanism called target-primed reverse transcription. LINES have been called "junk DNA," "viral DNA," and "selfish" DNA, and were once thought to be parasitic elements. However, LINES, which diversified before the emergence of many early vertebrates, has strongly shaped the evolution of eukaryotic genomes. This thesis will evaluate LINE abundance, diversity and activity in four anole lizards. An intrageneric analysis will be conducted using comparative phylogenetics and bioinformatics. Comparisons within the Anolis genus, which derives from a single lineage of an adaptive radiation, will be conducted to explore the relationship between LINE retrotransposon activity and causal changes in genomic size and composition.
ContributorsMay, Catherine (Author) / Kusumi, Kenro (Thesis advisor) / Gadau, Juergen (Committee member) / Rawls, Jeffery A (Committee member) / Arizona State University (Publisher)
Created2013
Description
Cancer is one of the most serious global diseases. We have focused on cancer immunoprevention. My thesis projects include developing a prophylactic primary and metastatic cancer vaccines, early cancer detection and investigation of genes involved in tumor development. These studies were focused on frame-shift (FS) antigens. The FS antigens are generated by genomic mutations or abnormal RNA processing, which cause a portion of a normal protein to be translated out of frame. The concept of the prophylactic cancer vaccine is to develop a general cancer vaccine that could prevent healthy people from developing different types of cancer. We have discovered a set of cancer specific FS antigens. One of the FS candidates, structural maintenance of chromosomes protein 1A (SMC1A) FS, could start to accumulate at early stages of tumor and be specifically exposed to the immune system by tumor cells. Prophylactic immunization with SMC1A-FS could significantly inhibit primary tumor development in different murine tumor models and also has the potential to inhibit tumor metastasis. The SMC1A-FS transcript was detected in the plasma of the 4T1/BALB/c mouse tumor model. The tumor size was correlated with the transcript ratio of the SMC1A-FS verses the WT in plasma, which could be measured by regular RT-PCR. This unique cancer biomarker has a practical potential for a large population cancer screen, as well as clinical tumor monitoring. With a set of mimotope peptides, antibodies against SMC1A-FS peptide were detected in different cancer patients, including breast cancer, pancreas cancer and lung cancer with a 53.8%, 56.5% and 12.5% positive rate respectively. This suggested that the FS antibody could be a biomarker for early cancer detection. The characterization of SMC1A suggested that: First, the deficiency of the SMC1A is common in different tumors and able to promote tumor initiation and development; second, the FS truncated protein may have nucleolus function in normal cells. Mis-control of this protein may promote tumor development. In summary, we developed a systematic general cancer prevention strategy through the variety immunological and molecular methods. The results gathered suggest the SMC1A-FS may be useful for the detection and prevention of cancer.
ContributorsShen, Luhui (Author) / Johnston, Stephen Albert (Thesis advisor) / Chang, Yung (Committee member) / Miller, Laurence (Committee member) / Sykes, Kathryn (Committee member) / Jacobs, Bertram (Committee member) / Arizona State University (Publisher)
Created2012
Description
The purpose of this study was to gather qualitative data on different and novel methods used to self-monitor diet and exercise during a weight loss study. Participants who used either a traditional paper and pencil method or a smart phone weight loss app for diet and exercise tracking were recruited for focus groups. Focus group discussions centered on the liked and disliked aspects of recording, perceived behavior changes, and suggestions for improved self-monitoring. Focus groups were organized based on the method of self-monitoring. The app group tracked calorie intake and expenditure via the "Lose It" app on their smart phones. The paper & pencil group recorded exercise and food intake in a journal and self-regulated diet based on recommended servings from each food group (or exchange lists). Focus group sessions were audio-recorded, transcribed and coded by the researcher and an independent coder. Results indicated that app participants liked the convenience, affordability, and user-friendly features, but wanted more nutrition advice. App participants liked self-managing their diet, not restricting certain foods or food groups and allowing for indulgences by balancing calories and exercise. Also, they desired an accurate estimation of energy expenditure from an app, based on individual characteristics (i.e., gender and age). Participants who recorded on paper liked the size for a visual layout of food entries, but desired a technology-enhanced method with an auto-calculation of calorie intake and expenditure. They also suggested increased accountability and opportunities for social support would enhance self-monitoring. Overall, an ideal technology-assisted self-monitoring app or program would be free and include an auto-calculation of calorie intake, a gender- and age- specific estimation of calories expended, easy entry of foods from a large database, the ability to enter whole recipes, nutrition information and recommendations, and be available via phone, tablet or computer (based on personal preference).
ContributorsSterner, Danielle (Author) / Wharton, Christopher (Christopher Mack), 1977- (Thesis advisor) / Johnston, Carol (Committee member) / Hall, Richard (Committee member) / Arizona State University (Publisher)
Created2012
Description
Teleosts have the most primitive adaptive immune system. However, in terms of functionality the teleost immune system is similar to birds and mammals. On the other hand, enteric bacterial pathogens of mammals and birds present conserved regulatory mechanisms that control virulence factors. In this context, deletion of conserved genes that control virulence factors have been successfully used as measure to construct live attenuated bacterial vaccines for mammals and birds. Here, I hypothesize that evolutionary conserved genes, which control virulence factors or are essential for bacterial physiology in Enterobacteriaceae, could be used as universal tools to design live attenuated recombinant bacterial vaccines from fish to mammals. The evolutionary conserved genes that control virulence factors, crp and fur, and the essential gene for the synthesis of the cell wall, asd, were studied in Edwardsiella ictaluri to develop a live recombinant vaccine for fish host. The genus Edwardsiella is one of the most ancient represent of the Enterobacteriaceae family. E. ictaluri, a host restricted pathogen of catfish (Ictalurus punctatus), is the causative agent of the enteric septicemia and one of the most important pathogens of this fish aquaculture. Although, crp and fur control different virulence factors in Edwardsiella, in comparison to other enterics, individual deletion of these genes triggered protective immune response at the systemic and mucosal level of the fish. Deletion of asdA gene allowed the creation of a balanced-lethal system to syntheses heterologous antigens. I concluded that crp, fur and asd could be universally used to develop live attenuate recombinant Enterobacteriaceae base vaccines for different hosts.
ContributorsSantander Morales, Javier Alonso (Author) / Curtiss, Roy Iii (Thesis advisor) / Chandler, Douglas (Committee member) / Chang, Yung (Committee member) / Shi, Yixin (Committee member) / Arizona State University (Publisher)
Created2012
Description
Birds have plasma glucose levels that are 1.5-2 times greater than mammals of similar body mass in addition to higher free fatty acid concentrations, both of which would typically impair endothelium-dependent vasodilation if observed in mammals. Endothelium-dependent vasodilation can be stimulated in mammals through the use of acetylcholine (ACh), which primarily acts through nitric oxide (NO) and cyclooxygenase (COX)-mediated pathways, with varying reliance on endothelial-derived hyperpolarizing factors (EDHFs). Very few studies have been conducted on small resistance systemic arteries from birds. The hypothesis was that because birds have naturally high glucose and free fatty acid concentrations, ACh-induced vasodilation of isolated arteries from mourning doves (Zenaida macroura) would be independent of endothelial-derived factors and resistant to high glucose-mediated vascular dysfunction. Small resistance mesenteric and cranial tibial (c. tibial) arteries were pre-constricted to 50% of resting inner diameter with phenyleprine then exposed to increasing doses of ACh (10-9 to 10-5 μM) or the NO donor, sodium nitroprusside (SNP; 10-12 to 10-3 μM). For both vessel beds, ACh-induced vasodilation occurred mainly through the activation of potassium channels, whereas vasodilation of mesenteric arteries additionally occurred through COX. Although arteries from both vessel beds fully dilated with exposure to sodium nitroprusside, ACh-mediated vasodilation was independent of NO. To examine the effect of high glucose on endothelium-dependent vasodilation, ACh dose response curves were conducted following exposure of isolated c. tibial arteries to either a control solution (20mM glucose) or high glucose (30mM). ACh-induced vasodilation was significantly impaired (p = 0.013) when exposed to high glucose, but normalized in subsequent vessels with pre-exposure to the superoxide dismutase mimetic tiron (10 mM). Superoxide concentrations were likewise significantly increased (p = 0.0072) following exposure to high glucose. These findings indicate that dove arteries do not appear to have endogenous mechanisms to counteract the deleterious effects of oxidative stress. Additional studies are required to assess whether endogenous mechanisms exist to protect avian vascular reactivity from systemic hyperglycemia.
ContributorsJarrett, Catherine Lee (Author) / Sweazea, Karen L (Thesis advisor) / Johnston, Carol (Committee member) / Gaesser, Glenn (Committee member) / Arizona State University (Publisher)
Created2012
Description
Background: Obesity is considered one of the most serious public health issues worldwide. Small, feasible lifestyle changes are necessary to obtain and maintain weight loss. Clinical evidence is inconclusive about whether meal preloading is an example of a small change that could potentially increase the likelihood of weight loss and weight maintenance. Objective: The aim of this study is to determine if consuming 23 grams of peanuts, as a meal preload, before a carbohydrate-rich meal will lower post prandial glycemia and insulinemia and increase satiety in the 2 hour period after a carbohydrate-rich meal. Design: 15 healthy, non-diabetic adults without any known peanut or tree nut allergies were recruited from a campus community. A randomized, 3x3 block crossover design was used. The day prior to testing participants refrained from vigorous activity and consumed a standard dinner meal followed by a 10 hour fast. Participants reported to the test site in the fasted state to complete one of three treatment meals: control (CON), peanut (NUT), or grain bar (BAR) followed one hour later by a carbohydrate-rich meal. Satiety, glucose and insulin were measured at different time points throughout the visit. Each participant had a one-week washout period between visits. Results: Glucose curves varied between treatments (p=.023). Blood glucose was significantly higher one hour after ingestion of the grain bar compared to the peanut and control treatments (p<.001). At 30 minutes after the meal, the control glucose was significantly higher than for the peanut or grain bar (p=.048). Insulin did vary significantly between treatments (p<.001). The insulin change one hour after grain bar consumption was significantly higher than after the peanut or control at the same time point (p<.001). The change in insulin one hour after peanut consumption was significantly higher than for the control treatment (p=.002). Overall satiety, expressed as the 180 minute AUC, differed significantly between treatments (p=.001). One hour after preload consumption, peanut and bar consumption was associated with greater satiety than the water control (p<.001). At 30 minutes post-meal, the grain bar was associated with greater satiety versus the water control (p=.049). The bar was also associated with greater satiety versus peanut and control at 60 and 90 minutes post-meal (p=.003 and .034, respectively). At 120 minutes post-meal, the final satiety measurement, the bar was still associated with greater satiety than the peanut preload (p=.023). Total energy intake, including test meal, on treatment days did not differ significantly between treatment (p=.233). Conclusions: Overall satiety, blood glucose and blood insulin levels differed at different time points depending on treatment. Both meal preloads increased overall satiety. However, grain bar ingestion resulted in sustained satiety, greater than the peanut preload. Grain bar ingestion resulted in an immediate glycemic and insulinemic response. However, the response was not sustained after the test meal was ingested. The results of this study suggest that a low-energy, carbohydrate-rich meal preload may have a positive impact on weight maintenance and weight loss by initiating a sustained increase in overall satiety. More research is needed to confirm these findings.
ContributorsFleming, Katie R (Author) / Johnston, Carol (Thesis advisor) / Wharton, Christopher (Christopher Mack), 1977- (Committee member) / Shepard, Christina (Committee member) / Arizona State University (Publisher)
Created2012
Description
The popularization of energy drink use as a supplement to exercise is steadily increasing, especially among young adult males. However, the effects of energy drinks on muscular performance in young adults have yet to be clearly elucidated. Eight male subjects (mean age: 23.3 ± 4.3 yrs, height: 181.0 ± 5.3 cm, fat percent 17.8 ± 5.2%, and weight 85.3 ± 12.6 kg) completed this randomized double-blinded cross over study. The purpose of this study was to determine differences in acute muscular strength and endurance and Profile of Mood States (POMS) scores between three treatments (RockStar, sugar-free RockStar, and sugar-free caffeine-free Placebo). It was hypothesized that there would be no significant differences in acute peak torque and endurance of the knee extensors and flexors or on fatigue and vigor subscores from the POMS questionnaire. Each man was tested randomly at least 1 week apart. Diet and time of day were held constant across trials. Peak torque of knee extensors and flexors at 60, 180, 240 degress/second and fatigue index and total work were calculated by performing 50 repetitions at 240 degrees/second. There were no significant differences in peak torque, fatigue index, or total work measures or in subjective measures of fatigue or vigor from the POMS between the treatments. This study indicates that RockStar energy drinks have no acute ergogenic effects in young men performing isokinetic strength or endurance testing.
ContributorsHawley, Michelle (Author) / Swan, Pamela (Thesis advisor) / Campbell, Kathryn (Committee member) / Johnston, Carol (Committee member) / Arizona State University (Publisher)
Created2012
Description
V(D)J recombination is responsible for generating an enormous repertoire of immunoglobulins and T cell receptors, therefore it is a centerpiece to the formation of the adaptive immune system. The V(D)J recombination process proceeds through two steps, site-specific cleavage at RSS (Recombination Signal Sequence) site mediated by the RAG recombinase (RAG1/2) and the subsequent imprecise resolution of the DNA ends, which is carried out by the ubiquitous non-homologous end joining pathway (NHEJ). The V(D)J recombination reaction is obliged to be tightly controlled under all circumstances, as it involves generations of DNA double strand breaks, which are considered the most dangerous lesion to a cell. Multifaceted regulatory mechanisms have been evolved to create great diversity of the antigen receptor repertoire while ensuring genome stability. The RAG-mediated cleavage reaction is stringently regulated at both the pre-cleavage stage and the post-cleavage stage. Specifically, RAG1/2 first forms a pre-cleavage complex assembled at the boarder of RSS and coding flank, which ensures the appropriate DNA targeting. Subsequently, this complex initiates site-specific cleavage, generating two types of double stranded DNA breaks, hairpin-ended coding ends (HP-CEs) and blunt signal ends (SEs). After the cleavage, RAG1/2 proteins bind and retain the recombination ends to form post-cleavage complexes (PCC), which collaborates with the NHEJ machinery for appropriate transfer of recombination ends to NHEJ for proper end resolution. However, little is known about the molecular basis of this collaboration, partly attributed to the lack of sensitive assays to reveal the interaction of PCC with HP-CEs. Here, for the first time, by using two complementary fluorescence-based techniques, fluorescence anisotropy and fluorescence resonance energy transfer (FRET), I managed to monitor the RAG1/2-catalyzed cleavage reaction in real time, from the pre-cleavage to the post-cleavage stages. By examining the dynamic fluorescence changes during the RAG-mediated cleavage reactions, and by manipulating the reaction conditions, I was able to characterize some fundamental properties of RAG-DNA interactions before and after cleavage. Firstly, Mg2+, known as a physiological cofactor at the excision step, also promotes the HP-CEs retention in the RAG complex after cleavage. Secondly, the structure of pre-cleavage complex may affect the subsequent collaborations with NHEJ for end resolution. Thirdly, the non-core region of RAG2 may have differential influences on the PCC retention of HP-CEs and SEs. Furthermore, I also provide the first evidence of RAG1-mediated regulation of RAG2. Our study provides important insights into the multilayered regulatory mechanisms, in modulating recombination events in developing lymphocytes and paves the way for possible development of detection and diagnotic markers for defective recombination events that are often associated immunodeficiency and/or lymphoid malignancy.
ContributorsWang, Guannan (Author) / Chang, Yung (Thesis advisor) / Levitus, Marcia (Committee member) / Misra, Rajeev (Committee member) / Anderson, Karen (Committee member) / Arizona State University (Publisher)
Created2012
Description
Skeletal muscles arise from the myotome compartment of the somites that form during vertebrate embryonic development. Somites are transient structures serve as the anlagen for the axial skeleton, skeletal muscle, tendons, and dermis, as well as imposing the metameric patterning of the axial musculoskeletal system, peripheral nerves, and vasculature. Classic studies have described the role of Notch, Wnt, and FGF signaling pathways in controlling somite formation and muscle formation. However, little is known about the transformation of myotome compartments into identifiable post-natal muscle groups. Using a mouse model, I have undertaken an evaluation of morphological events, including hypertrophy and hyperplasia, related to the formation of several muscles positioned along the dorsal surface of the vertebrae and ribs. Lunatic fringe (Lfng) deficient embryos and neonates were also examined to further understand the role of the Notch pathway in these processes as it is a modulator of the Notch receptor and plays an important role in defining somite borders and anterior-posterior patterning in many vertebrates. Lunatic fringe deficient embryos showed defects in muscle fiber hyperplasia and hypertrophy in the iliocostalis and longissimus muscles of the erector spinae group. This novel data suggests an additional role for Lfng and the Notch signaling pathway in embryonic and fetal muscle development.
ContributorsDe Ruiter, Corinne (Author) / Rawls, J. Alan (Thesis advisor) / Wilson-Rawls, Jeanne (Committee member) / Kusumi, Kenro (Committee member) / Fisher, Rebecca E. (Committee member) / Arizona State University (Publisher)
Created2012
Description
Determining the factors associated with the availability of healthy and unhealthy foods in the household may help in understanding the varying complexities that contribute to obesity among children and help design interventions to impact children's food consumption behaviors. This study examined factors that are associated with the availability of healthy and unhealthy foods in children's home food environments (HFE). Data was collected from a random-digit-dial telephone survey of 1708 households, with at least one child between 3-18 years of age, located in five low-income New Jersey cities. HFE was assessed based on responses to a set of six items that measured availability of specific healthy and unhealthy foods in the respondent's home. These items contributed to construction of three HFE scales used as dependent variables in these analyses: healthy HFE, unhealthy HFE, and a ratio of healthy to unhealthy foods in the HFE. Independent variables included household socio-demographics, parental perceptions of their own weight and diet health, frequency of family meals, proximity to food outlets, and perception of access to healthy foods in the neighborhood food environment. Significant differences were observed in the HFE by race and ethnicity, with Non-Hispanic black children having fewer healthy foods and Non-Hispanic white children having more unhealthy food items available at home. Parents who reported being overweight or obese had a healthier HFE and those perceiving their own eating as healthy had more healthy and less unhealthy foods in the household. Food-secure households had more unhealthy compared to healthy foods at home. Households located farther from a supermarket had a greater number of unhealthy food items and a lower healthy/unhealthy food availability ratio. Parental perception of better access to fruits and vegetables and low-fat foods was associated with availability of a greater number of healthy food items at home. Overall, the HFE varied by parental and demographic characteristics, parental perceptions about the food environment and the actual features of the built neighborhood food environment.
ContributorsBerry, Andrea (Author) / Ohri-Vachaspati, Punam (Thesis advisor) / Johnston, Carol (Committee member) / Wharton, Christopher (Christopher Mack), 1977- (Committee member) / Arizona State University (Publisher)
Created2012