Matching Items (70)
Description
Alzheimer's disease (AD) is the leading neurodegenerative disease, affecting roughly 8% of people 65 years of age or older. There exists an imperative need to develop a non-invasive test for the earlier detection of AD. The use of biomarkers is a promising option that examines the toxic mechanisms and metabolic pathways that cause Alzheimer's disease, eventually leading to an early diagnostic method. This thesis presents the use of oligomeric beta-amyloid as a biomarker to detect Alzheimer's disease via a specialized enzyme-linked protein assay. Specifically, this paper details the optimization and development of a novel phage capture enzyme-linked immunosorbent assay (ELISA) that can detect the relative quantity of beta-amyloid oligomers in samples from a mouse model of AD. The objective of this thesis was to optimize a phage capture ELISA using the A4 single-chain variable fragment (scFv) to quantify the amount of beta-amyloid oligomers in various mice samples. A4 selectively recognizes a toxic oligomeric form of beta-amyloid. The level of A4-reactive oligomeric beta-amyloid was measured in triplicate in homogenized mouse brain tissue samples from eight transgenic (TG) and eight nontransgenic (NTG) animals aged five, nine, and thirteen months. There was a significant difference (p < 0.0005) between the five month TG and NTG mice. A decrease in beta-amyloid levels with the aging of the TG mice suggested that the beta-amyloid oligomers may be aggregating to form beta-amyloid fibrils. Conversely, the quantity of beta-amyloid increased with the aging of the NTG mice. This indicated that beta-amyloid oligomers may develop with normal aging.
ContributorsBrownlee, Taylor (Author) / Sierks, Michael (Thesis advisor) / Williams, Stephanie (Committee member) / Xin, Wei (Committee member) / Arizona State University (Publisher)
Created2013
Description
Salmonella enterica is a gastrointestinal (GI) pathogen that can cause systemic diseases. It invades the host through the GI tract and can induce powerful immune responses in addition to disease. Thus, it is considered as a promising candidate to use as oral live vaccine vectors. Scientists have been making great efforts to get a properly attenuated Salmonella vaccine strain for a long time, but could not achieve a balance between attenuation and immunogenicity. So the regulated delayed attenuation/lysis Salmonella vaccine vectors were proposed as a design to seek this balance. The research work is progressing steadily, but more improvements need to be made. As one of the possible improvements, the cyclic adenosine monophosphate (cAMP) -independent cAMP receptor protein (Crp*) is expected to protect the Crp-dependent crucial regulator, araC PBAD, in these vaccine designs from interference by glucose, which decreases synthesis of cAMP, and enhance the colonizing ability by and immunogenicity of the vaccine strains. In this study, the cAMP-independent crp gene mutation, crp-70, with or without araC PBAD promoter cassette, was introduced into existing Salmonella vaccine strains. Then the plasmid stability, growth rate, resistance to catabolite repression, colonizing ability, immunogenicity and protection to challenge of these new strains were compared with wild-type crp or araC PBAD crp strains using western blots, enzyme-linked immunosorbent assays (ELISA) and animal studies, so as to evaluate the effects of the crp-70 mutation on the vaccine strains. The performances of the crp-70 strains in some aspects were closed to or even exceeded the crp+ strains, but generally they did not exhibit the expected advantages compared to their wild-type parents. Crp-70 rescued the expression of araC PBAD fur from catabolite repression. The strain harboring araC PBAD crp-70 was severely affected by its slow growth, and its colonizing ability and immunogenicity was much weaker than the other strains. The Pcrp crp-70 strain showed relatively good ability in colonization and immune stimulation. Both the araC PBAD crp-70 and the Pcrp crp-70 strains could provide certain levels of protection against the challenge with virulent pneumococci, which were a little lower than for the crp+ strains.
ContributorsShao, Shihuan (Author) / Curtiss, Roy (Thesis advisor) / Arizona State University (Publisher)
Created2012
Description
Cancer remains one of the leading killers throughout the world. Death and disability due to lung cancer in particular accounts for one of the largest global economic burdens a disease presents. The burden on third-world countries is especially large due to the unusually large financial stress that comes from late tumor detection and expensive treatment options. Early detection using inexpensive techniques may relieve much of the burden throughout the world, not just in more developed countries. I examined the immune responses of lung cancer patients using immunosignatures – patterns of reactivity between host serum antibodies and random peptides. Immunosignatures reveal disease-specific patterns that are very reproducible. Immunosignaturing is a chip-based method that has the ability to display the antibody diversity from individual sera sample with low cost. Immunosignaturing is a medical diagnostic test that has many applications in current medical research and in diagnosis. From a previous clinical study, patients diagnosed for lung cancer were tested for their immunosignature vs. healthy non-cancer volunteers. The pattern of reactivity against the random peptides (the ‘immunosignature’) revealed common signals in cancer patients, absent from healthy controls. My study involved the search for common amino acid motifs in the cancer-specific peptides. My search through the hundreds of ‘hits’ revealed certain motifs that were repeated more times than expected by random chance. The amino acids that were the most conserved in each set include tryptophan, aspartic acid, glutamic acid, proline, alanine, serine, and lysine. The most overall conserved amino acid observed between each set was D - aspartic acid. The motifs were short (no more than 5-6 amino acids in a row), but the total number of motifs I identified was large enough to assure significance. I utilized Excel to organize the large peptide sequence libraries, then CLUSTALW to cluster similar-sequence peptides, then GLAM2 to find common themes in groups of peptides. In so doing, I found sequences that were also present in translated cancer expression libraries (RNA) that matched my motifs, suggesting that immunosignatures can find cancer-specific antigens that can be both diagnostic and potentially therapeutic.
ContributorsShiehzadegan, Shima (Author) / Johnston, Stephen (Thesis director) / Stafford, Phillip (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2015-12
Description
The influenza virus, also known as "the flu", is an infectious disease that has constantly affected the health of humanity. There is currently no known cure for Influenza. The Center for Innovations in Medicine at the Biodesign Institute located on campus at Arizona State University has been developing synbodies as a possible Influenza therapeutic. Specifically, at CIM, we have attempted to design these initial synbodies to target the entire Influenza virus and preliminary data leads us to believe that these synbodies target Nucleoprotein (NP). Given that the synbody targets NP, the penetration of cells via synbody should also occur. Then by Western Blot analysis we evaluated for the diminution of NP level in treated cells versus untreated cells. The focus of my honors thesis is to explore how synthetic antibodies can potentially inhibit replication of the Influenza (H1N1) A/Puerto Rico/8/34 strain so that a therapeutic can be developed. A high affinity synbody for Influenza can be utilized to test for inhibition of Influenza as shown by preliminary data. The 5-5-3819 synthetic antibody's internalization in live cells was visualized with Madin-Darby Kidney Cells under a Confocal Microscope. Then by Western Blot analysis we evaluated for the diminution of NP level in treated cells versus untreated cells. Expression of NP over 8 hours time was analyzed via Western Blot Analysis, which showed NP accumulation was retarded in synbody treated cells. The data obtained from my honors thesis and preliminary data provided suggest that the synthetic antibody penetrates live cells and targets NP. The results of my thesis presents valuable information that can be utilized by other researchers so that future experiments can be performed, eventually leading to the creation of a more effective therapeutic for influenza.
ContributorsHayden, Joel James (Author) / Diehnelt, Chris (Thesis director) / Johnston, Stephen (Committee member) / Legutki, Bart (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2014-05
Description
Thirty six percent of Americans are obese and thirty three percent are overweight; obesity has become a known killer in the U.S. yet its prevalence has maintained a firm grasp on the U.S. population and continues to spread across the globe as other countries slowly adopt the American lifestyle. A survey was compiled collecting demographic and body mass index (BMI) information, as well as Tanofsky-Kraff’s (2009) “Assess Eating in the Absence of Hunger” survey questions. The survey used for this study was emailed out to Arizona State University students in Barrett, The Honors College, and the ASU School of Nutrition and Health Promotion listservs. A total of 457 participants completed the survey, 72 males and 385 females (mean age, 24.5±7.7 y; average body mass index (BMI), 23.4 ± 4.8 [a BMI of 25-29.9 is classified as overweight]). When comparing BMI with the living situation, 71% of obese students were living at home with family versus off campus with friends or alone. For comparison, 45% of normal weight students lived at home with family. These data could help structure prevention plans targeting college students by focusing on weight gain prevention at the family level. Results from the Tanofsky-Kraff (2009) survey revealed there was not a significant relationship between external or physical cues and BMI in men or women, but there was a significant positive correlation between emotional cues and BMI in women only. Anger and sadness were the emotional cues in women related to initiating consumption past satiation and consumption following several hours of fasting. Although BMI was inversely related to physical activity in this sample (r = -0.132; p=0.005), controlling for physical activity did not impact the significant associations of BMI with anger or sadness (P>0.05). This information is important in targeting prevention programs to address behavioral change and cognitive awareness of the effects of emotion on over-consumption.
ContributorsGarza, Andrea Marie (Author) / Johnston, Carol (Thesis director) / Jacobs, Mark (Committee member) / Coletta, Dawn (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor) / School of Life Sciences (Contributor)
Created2013-05
Description
New-onset diabetes after kidney transplantation (NODAT) occurs in 20% of kidney transplant patients. In 5 patients who are at risk for new-onset diabetes after kidney transplantation, skeletal muscle gene expression profiling was performed both before and after kidney transplant. The differences in gene expression before and after transplant were compared in order to identify specific genes that could be linked to developing NODAT. These findings could open new avenues for future research.
ContributorsLowery, Clint Curtis (Author) / Coletta, Dawn (Thesis director) / Katsanos, Christos (Committee member) / Willis, Wayne (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / W. P. Carey School of Business (Contributor)
Created2014-05
Description
DNA methylation, a subset of epigenetics, has been found to be a significant marker associated with variations in gene expression and activity across the entire human genome. As of now, however, there is little to no information about how DNA methylation varies between different tissues inside a singular person's body. By using research data from a preliminary study of lean and obese clinical subjects, this study attempts to put together a profile of the differences in DNA methylation that can be observed between two particular body tissues from this subject group: blood and skeletal muscle. This study allows us to start describing the changes that occur at the epigenetic level that influence how differently these two tissues operate, along with seeing how these tissues change between individuals of different weight classes, especially in the context of the development of symptoms of Type 2 Diabetes.
ContributorsRappazzo, Micah Gabriel (Author) / Coletta, Dawn (Thesis director) / Katsanos, Christos (Committee member) / Dinu, Valentin (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor) / Department of Psychology (Contributor)
Created2013-12
DescriptionA novel and unconventional approach for delivering a eukaryotic apoptosis factor, TNF-related apoptosis-inducing ligand (TRAIL), to cancer cells within and around necrotizing tumors by utilizing a S. Typhimurium purine requiring auxotroph as a biological vector to develop two anticancer therapies with multiple modality and broad economic feasibility.
ContributorsKoons, Andrew (Author) / Curtiss, Roy (Thesis director) / Lake, Douglas (Committee member) / Janthakahalli, Nagaraj Vinay (Committee member) / Barrett, The Honors College (Contributor)
Created2013-12
Description
In this study, we demonstrate the effectiveness of a cancer type specific FrAmeShifT (FAST) vaccine. A murine breast cancer (mBC) FAST vaccine and a murine pancreatic cancer (mPC) FAST vaccine were tested in the 4T1 breast cancer syngeneic mouse model. The mBC FAST vaccine, both with and without check point inhibitors (CPI), significantly slowed tumor growth, reduced pulmonary metastasis and increased the cell-mediated immune response. In terms of tumor volumes, the mPC FAST vaccine was comparable to the untreated controls. However, a significant difference in tumor volume did emerge when the mPC vaccine was used with CPI. The collective data indicated that the immune checkpoint blockade therapy was only beneficial with suboptimal neoantigens. More importantly, the FAST vaccine, though requiring notably less resources, performed similarly to the personalized version of the frameshift breast cancer vaccine in the same mouse model. Furthermore, because the frameshift peptide (FSP) array provided a strong rationale for a focused vaccine, the FAST vaccine can theoretically be expanded and translated to any human cancer type. Overall, the FAST vaccine is a promising treatment that would provide the most benefit to patients while eliminating most of the challenges associated with current personal cancer vaccines.
ContributorsMurphy, Sierra Nicole (Author) / Johnston, Stephen (Thesis director) / Peterson, Milene (Committee member) / School of Mathematical and Statistical Sciences (Contributor) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
The goal of this paper is to discuss the most efficient method to achieve early detection in lung cancers by reducing the occurrences of false-positive readings. Imaging techniques (computed tomography screenings) have greater impact than non-imaging techniques in early detection for lung cancer. On the other hand, positron emission tomography and non-imaging techniques, such as liquid biopsy, are better at distinguishing cancer stages. Therefore, these techniques are not suitable early detection methods for lung cancer. Based on literature reviews, the combination that is most capable of early lung cancer detection incorporate low-dose computed tomography screenings, thin-section computed tomography screenings, and computer-aided diagnosis. Low-dose computed tomography screenings has lower radiation-associated risks compared to the standard-dose computed tomography. This technique can be used as both at the first examination and the follow-up examinations. Thin-section computed tomography screenings can be used as a supplement to check if there is any nodules that have not yet been discovered. Computer-aided diagnosis is an add-on method to make sure the computed tomography screenings images are being correctly labeled. Identifying other contributing factors to the effectiveness of the early lung cancer detection, such as the amount of forced expiratory volume, forced vital capacity, and the presence of emphysema, could also decrease the percentage of false positive outcomes.
ContributorsChuang, Hao-Yun (Author) / Johnston, Stephen (Thesis director) / Peterson, Milene (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05