Matching Items (13)
Filtering by
- All Subjects: Synthetic Biology
- Creators: Department of Chemistry and Biochemistry
- Creators: Harrington Bioengineering Program
- Resource Type: Text
Description
Walking interventions focused on increasing step counts are typically associated with salutary effects on glycemia, fasting insulin, insulin resistance and blood lipids which may be in turn associated with improvements in cardiorespiratory fitness (peak oxygen uptake – VO2peak) and vascular stiffness. We hypothesized that a novel 4-month, behavioral economics-based walking intervention would have favorable effects on glucose homeostasis and blood lipids and that these in turn would be related to VO2peak and vascular stiffness (carotid femoral pulse wave velocity – cfPWV).
We carried out secondary analyses on a subsample of sedentary, overweight/obese adults who participated in a 4-month, 2x2, randomized-controlled walking intervention examining the effects of goal setting (static v. adaptive goals) and rewards (immediate v. delayed) on steps/day (N=96). Fasting blood samples (n=58) were collected from participants before and after the intervention. Premenopausal females were in the follicular phase of their menstrual cycles. Lipid and glucose levels were measured using an automated chemistry analyzer, while insulin was measured using radio-immunoassay. Homeostatic model of insulin resistance (HOMA-IR) was calculated using the following formula (HOMA-IR=glucose x insulin / 405). We examined associations [partial correlations (adjusted for age)] between changes in blood biomarkers and VO2peak and cfPWV, irrespective of group, and we used linear mixed models to examine between-group differences in levels of and change in biomarker outcomes.
Groups did not differ in overall levels of, or degree of change in, biomarker outcomes (all p>0.05). Mean changes, irrespective of group, in biomarkers were as follows: glucose Δ= 0.74± 4.5mg/dl; insulin Δ= 0.09 ± 4.1 µU/ml; total cholesterol Δ= 0.24 ± 20.6 mg/dl; HDL-C Δ= 0.27 ± 5.1 mg/dl; LDL-C Δ= 1.3 ± 19.9 mg/dl; triglycerides Δ= 1.7 ± 27.2 mg/dl; HOMA-IR Δ = -.0548 ± 1.05). We found no significant associations between change in biomarker levels and change in VO2peak or change in cfPWV (all correlation coefficients < 0.15; p > 0.05).
A 4-month, behavioral economics-based mHealth intervention focused on increasing steps/day did not bring about favorable changes on markers of glycemia, insulin resistance and blood lipids.
We carried out secondary analyses on a subsample of sedentary, overweight/obese adults who participated in a 4-month, 2x2, randomized-controlled walking intervention examining the effects of goal setting (static v. adaptive goals) and rewards (immediate v. delayed) on steps/day (N=96). Fasting blood samples (n=58) were collected from participants before and after the intervention. Premenopausal females were in the follicular phase of their menstrual cycles. Lipid and glucose levels were measured using an automated chemistry analyzer, while insulin was measured using radio-immunoassay. Homeostatic model of insulin resistance (HOMA-IR) was calculated using the following formula (HOMA-IR=glucose x insulin / 405). We examined associations [partial correlations (adjusted for age)] between changes in blood biomarkers and VO2peak and cfPWV, irrespective of group, and we used linear mixed models to examine between-group differences in levels of and change in biomarker outcomes.
Groups did not differ in overall levels of, or degree of change in, biomarker outcomes (all p>0.05). Mean changes, irrespective of group, in biomarkers were as follows: glucose Δ= 0.74± 4.5mg/dl; insulin Δ= 0.09 ± 4.1 µU/ml; total cholesterol Δ= 0.24 ± 20.6 mg/dl; HDL-C Δ= 0.27 ± 5.1 mg/dl; LDL-C Δ= 1.3 ± 19.9 mg/dl; triglycerides Δ= 1.7 ± 27.2 mg/dl; HOMA-IR Δ = -.0548 ± 1.05). We found no significant associations between change in biomarker levels and change in VO2peak or change in cfPWV (all correlation coefficients < 0.15; p > 0.05).
A 4-month, behavioral economics-based mHealth intervention focused on increasing steps/day did not bring about favorable changes on markers of glycemia, insulin resistance and blood lipids.
ContributorsHook, Benjamin E. (Author) / Angadi, Siddhartha (Thesis director) / Gaesser, Glenn (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Exercise is a great boon to both the health of individuals and the national as a whole. Exercise provides a wide range of significant and well established benefits to both physical and psychological health, with many benefits that are still being discovered. The effects of exercise on health are somewhat unique, as exercise is one of a limited number of ways to improve health that is not harm a reduction strategy, but instead increases health through direct benefit, rather than increasing health by decreasing damage and harm. Support is also given to the proposal that individuals are in best position to determine the intensity of exercise and to choose primary activities to participate in, in order to provide near maximum physical and psychological benefit, with the understanding that frequency of exercise is of the upmost importance for benefit. The accessibility of exercise and the tremendous health benefit of exercise, makes exercise a huge asset in reducing the exorbitant health care spending and improving mediocre health outcomes in this country; a reasonable goal as numerous countries have better health the United States, even though the United States spends the more than any other country on health.
ContributorsRael, Ashur Scott (Author) / Kashiwagi, Dean (Thesis director) / Kashiwagi, Jacob (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Film, Dance and Theatre (Contributor)
Created2015-05
Description
Bacteria have been shown to possess a large array of regulatory mechanisms to not just respond to a diverse array of environmental stresses, but to injurious artificial proteins as well. A previous investigation introduced DX, a man-made ATP sequestering protein into Escherichia coli (E. coli) which resulted in the formation of novel endoliposome structures and induced a viable but non-culturable state (VBNC) that was not easily reversed. It was hypothesized that the broadly conserved bacterial stringent response pathway may have been responsible for the observed phenotypic changes. With the goal of unveiling the molecular mechanism behind this novel response, changes in cellular morphology and physiology upon DX expression were assessed in a population of E. coli encoding a dysfunctional relA gene, one of the two genes controlling the induction of the stringent response. It was ultimately shown that RelA directly contributed to cellular filamentation, endoliposome structure formation, and the induction of a VBNC state. While the stringent response has been extensively shown to induce a VBNC state, to our knowledge, relA has not yet been shown to induce filamentation or coordinate the formation of endoliposome structures in bacteria. As the stringent response has been shown to be increasingly involved in antibiotic tolerance, this study provided an exciting opportunity to further characterize this adaptive response pathway to aid in the future development of novel therapeutics. In addition to this, this study continued to highlight that the DX protein may serve one of the first tools to allow for the direct selection of bacteria in a VBNC state by morphologically distinguishing non-culturable cells through cellular filamentation.
ContributorsFrost, Fredrick Charles (Author) / Chaput, John (Thesis director) / Wachter, Rebekka (Committee member) / Korch, Shaleen (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2014-12
Description
Nucleic acids encode the information required to create life, and polymerases are the gatekeepers charged with maintaining the storage and flow of this genetic information. Synthetic biologists utilize this universal property to modify organisms and other systems to create unique traits or improve the function of others. One of the many realms in synthetic biology involves the study of biopolymers that do not exist naturally, which is known as xenobiology. Although life depends on two biopolymers for genetic storage, it may be possible that alternative molecules (xenonucleic acids – XNAs), could be used in their place in either a living or non-living system. However, implementation of an XNA based system requires the development of polymerases that can encode and decode information stored in these artificial polymers. A strategy called directed evolution is used to modify or alter the function of a protein of interest, but identifying mutations that can modify polymerase function is made problematic by their size and overall complexity. To reduce the amount of sequence space that needs to be samples when attempting to identify polymerase variants, we can try to make informed decisions about which amino acid residues may have functional roles in catalysis. An analysis of Family B polymerases has shown that residues which are involved in substrate specificity are often highly conserved both at the sequence and structure level. In order to validate the hypothesis that a strong correlation exists between structural conservation and catalytic activity, we have selected and mutated residues in the 9°N polymerase using a loss of function mutagenesis strategy based on a computational analysis of several homologues from a diverse range of taxa. Improvement of these models will hopefully lead to quicker identification of loci which are ideal engineering targets.
ContributorsHaeberle, Tyler Matthew (Author) / Chaput, John (Thesis director) / Chen, Julian (Committee member) / Larsen, Andrew (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
Transgene expression in mammalian cells has been shown to meet resistance in the form of silencing due to chromatin buildup within the cell. Interactions of proteins with chromatin modulate gene expression profiles. Synthetic Polycomb transcription factor (PcTF) variants have the potential to reactivate these silence transgenes as shown in Haynes & Silver 2011. PcTF variants have been constructed via TypeIIS assembly to further investigate this ability to reactive transgenes. Expression in mammalian cells was confirmed via fluorescence microscopy and red fluorescent protein (RFP) expression in cell lysate. Examination of any variation in conferment of binding strength of homologous Polycomb chromodomains (PCDs) to its trimethylated lysine residue target on histone three (H3K27me3) was investigated using a thermal shift assay. Results indicate that PcTF may not be a suitable protein for surveying with SYPRO Orange, a dye that produces a detectable signal when exposed to the hydrophobic domains of the melting protein. A cell line with inducible silencing of a chemiluminescent protein was used to determine the effects PcTF variants had on gene reactivation. Results show down-regulation of the target reporter gene. We propose this may be due to PcTF not binding to its target; this would cause PcTF to deplete transcriptional machinery in the nucleus. Alternatively, the CMV promoter could be sequestering transcriptional machinery in its hyperactive transcription of PcTF leading to widespread down-regulation. Finally, the activation domain used may not be appropriate for this cell type. Future PcTF variants will address these hypotheses by including multiple Polycomb chromodomains (PCDs) to alter the binding dynamics of PcTF to its target, and by incorporating alternative promoters and activation domains.
ContributorsGardner, Cameron Lee (Author) / Haynes, Karmella (Thesis director) / Stabenfeldt, Sarah (Committee member) / Barrett, The Honors College (Contributor) / Department of Finance (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05
Description
Physical activity as a health or nutrition related intervention might stimulate appetite and increase hunger due to increased energy expenditure. This study analyzed the effect of a postprandial 15-minute walk on the hunger and energy intake of 10 obese, pre-diabetic adults. Subjects participated in three 4-hour trials: a walk treatment (consume highly glycemic meal, walk for 15 minutes at a moderate pace, and rest for 4 hours), a fiber treatment (consume highly glycemic meal enriched with soluble fiber and rest for 4 hours), and a control treatment (consume highly glycemic meal without fiber and rest for 4 hours). The effects of each treatment on hunger and energy intake were measured using a Likert scale analysis (ranging from "completely satisfied" to "extremely hungry") at 4 hours post-treatment and pre/ post 24-hour dietary logs. The results showed no significant increase or decrease on hunger or energy intake for both the walk and the fiber treatment compared to the control treatment. This denies the idea that physical activity might increase short-term hunger, and supports the use of physical activity as a viable nutrition related intervention tool.
ContributorsTerrell, Alayna Franci (Author) / Johnston, Carol (Thesis director) / Vega Lopez, Sonia (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2015-05
Description
Currently in synthetic biology only the Las, Lux, and Rhl quorum sensing pathways have been adapted for broad engineering use. Quorum sensing allows a means of cell to cell communication in which a designated sender cell produces quorum sensing molecules that modify gene expression of a designated receiver cell. While useful, these three quorum sensing pathways exhibit a nontrivial level of crosstalk, hindering robust engineering and leading to unexpected effects in a given design. To address the lack of orthogonality among these three quorum sensing pathways, previous scientists have attempted to perform directed evolution on components of the quorum sensing pathway. While a powerful tool, directed evolution is limited by the subspace that is defined by the protein. For this reason, we take an evolutionary biology approach to identify new orthogonal quorum sensing networks and test these networks for cross-talk with currently-used networks. By charting characteristics of acyl homoserine lactone (AHL) molecules used across quorum sensing pathways in nature, we have identified favorable candidate pathways likely to display orthogonality. These include Aub, Bja, Bra, Cer, Esa, Las, Lux, Rhl, Rpa, and Sin, which we have begun constructing and testing. Our synthetic circuits express GFP in response to a quorum sensing molecule, allowing quantitative measurement of orthogonality between pairs. By determining orthogonal quorum sensing pairs, we hope to identify and adapt novel quorum sensing pathways for robust use in higher-order genetic circuits.
ContributorsMuller, Ryan (Author) / Haynes, Karmella (Thesis director) / Wang, Xiao (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
Synthetic biology is an emerging engineering disciple, which designs and controls biological systems for creation of materials, biosensors, biocomputing, and much more. To better control and engineer these systems, modular genetic components which allow for highly specific and high dynamic range genetic regulation are necessary. Currently the field struggles to demonstrate reliable regulators which are programmable and specific, yet also allow for a high dynamic range of control. Inspired by the characteristics of the RNA toehold switch in E. coli, this project attempts utilize artificial introns and complementary trans-acting RNAs for gene regulation in a eukaryote host, S. cerevisiae. Following modification to an artificial intron, splicing control with RNA hairpins was demonstrated. Temperature shifts led to increased protein production likely due to increased splicing due to hairpin loosening. Progress is underway to demonstrate trans-acting RNA interaction to control splicing. With continued development, we hope to provide a programmable, specific, and effective means for translational gene regulation in S. cerevisae.
ContributorsDorr, Brandon Arthur (Author) / Wang, Xiao (Thesis director) / Green, Alexander (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
With obesity and metabolic diseases reaching epidemic levels, it is important to find ways to increase physical activity and improve diet. Previous studies have shown that improvements in mood can increase desire to perform physical activity, and that vitamin C intake is linked to improvements in mood. Based on this, two hypotheses were formed and tested to investigate the effect on physical activity levels and mood states from vitamin C supplementation at a dose of one gram per day in the form of a novel functional food. Thirty-one college students or faculty at Arizona State University were screened from a pool of applicants and placed into either a vitamin C or placebo group; all participants received the novel functional food to eat daily for four weeks. Serum levels of vitamin C, weight, height, BMI, body fat percentage, mood, and physical activity were measured before and after the functional food intervention. Vitamin C changed significantly through the course of the study in the experimental group. Baseline data for participants showed a positive correlation between vitamin C status and vigor, and a negative correlation between vitamin C status and weight and BMI. Physical activity was not related to vitamin C status, according to baseline data, and it did not significantly change over the course of the study. The results indicate that variance in BMI can be attributed to vitamin C status, but the study should be refined and tested again.
ContributorsHelland, Stephanie Lynn (Author) / Johnston, Carol (Thesis director) / Sweazea, Karen (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / Department of Psychology (Contributor) / School of Life Sciences (Contributor) / Graduate College (Contributor)
Created2014-05
Description
Sickle Cell Disease (SCD) is a prevalent genetic disease in Africa, and specifically in Kenya. The lack of available relevant disease education and screening mean that most don't understand the importance of getting testing and many children die before they can get prophylactic care. This project was designed to address the lack of knowledge with supplemental educational materials to be partnered with an engineering capstone project that provides a low cost diagnostic test.
ContributorsShawver, Jamie Christine (Author) / Caplan, Michael (Thesis director) / Snyder, Jan (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05