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- All Subjects: Genetics
- All Subjects: Diabetes
- Creators: School of Life Sciences
- Creators: Sweazea, Karen
- Resource Type: Text
Description
ABSTRACT This randomized, controlled, double-blind crossover study examined the effects of a preprandial, 20g oral dose of apple cider vinegar (ACV) on colonic fermentation and glycemia in a normal population, with the ultimate intention of identifying the mechanisms by which vinegar has been shown to reduce postprandial glycemia and insulinemia. Fifteen male and female subjects were recruited, ages 20-60y, who had no prior history of gastrointestinal (GI) disease or resections impacting normal GI function, were non-smokers, were non-vegetarian/vegan, were not taking any medications known to alter (glucose) metabolism, and were free of chronic disease including diabetes. Subjects were instructed to avoid exercise, alcohol and smoking the day prior to their trials and to consume a standardized, high-carbohydrate dinner meal the eve prior. There was a one-week washout period per subject between appointments. Breath hydrogen, serum insulin and capillary glucose were assessed over 3 hours after a high-starch breakfast meal to evaluate the impact of preprandial supplementation with ACV or placebo (water). Findings confirmed the antiglycemic effects of ACV as documented in previous studies, with significantly lower mean blood glucose concentrations observed during ACV treatment compared to the placebo at 30 min (p=0.003) and 60 min (p=0.005), and significantly higher mean blood glucose concentrations at 180 min (p=0.045) postprandial. No significant differences in insulin concentrations between treatments. No significant differences were found between treatments (p>0.05) for breath hydrogen; however, a trend was observed between the treatments at 180 min postprandial where breath hydrogen concentration was visually perceived as being higher with ACV treatment compared to the placebo. Therefore, this study failed to support the hypothesis that preprandial ACV ingestion produces a higher rate of colonic fermentation within a 3 hour time period following a high-carbohydrate meal. Due to variations in experiment duration noted in other literature, an additional study of similar nature with an expanded specimen collections period, well beyond 3 hours, is warranted.
ContributorsMedved, Emily M (Author) / Johnston, Carol (Thesis advisor) / Sweazea, Karen (Committee member) / Shepard, Christina (Committee member) / Arizona State University (Publisher)
Created2012
Description
This study focused on the connection between the EnvZ/OmpR two-component regulatory system and the iron homeostasis system in Escherichia coli, specifically how a mutant form of EnvZ11/OmpR is able to reduce the expression of fepA::lacZ, a reporter gene fusion in E. coli. FepA is one of several outer membrane siderophore receptors that allow extracellular siderophores bound to iron to enter the cells to power various biological processes. Previous studies have shown that in E. coli cells that expressed a mutant allele of envZ, called envZ11, which led to altered expression of various iron genes including down regulation of fepA::lacZ. The wild type EnvZ/OmpR system is not considered to regulate iron genes, but because these envz11 strains had downregulated fepA::lacZ, this study was undertaken to understand the connection and mechanisms of this downregulation. A large number of Lac+ revertants were obtained from the B32-2483 strain (envz11 and fepA::lacZ) and 7 Lac+ revertants that had reversion mutations not directly correcting the envZ11 allele were further characterized. With P1 phage transduction genetic mapping that involved moving a kanamycin resistance marker linked to fepA::lacZ, two Lac+ revertants were found to have their reversion mutations in the fepA promoter region, while the other five revertants had their mutations mapping outside the fepA region. These two revertants underwent DNA sequencing and found to carry two different single base pair mutations in two different locations of the fepA promoter region. Each one is in the Fur repressor binding region, but one also may have affected the Shine-Dalgarno region involved in translation initiation. All 7 reveratants underwent beta-galactosidase assays to measure fepA::lacZ expression. The two revertants that had mutations in the fepA promoter region had significantly increased fepA activity, with the revertant with the Shine-Dalgarno mutation having the most elevated fepA expression. The other 5 revertants that did not map in the fepA region had fepA expression elevated to the same level as that found in the wild type EnvZ/OmpR background. The data suggest that the negative effect of envZ11 can be overcome by multiple mechanisms, including directly correcting the envZ11 allele or changing the fepA promoter region.
ContributorsKalinkin, Victor Arkady (Co-author) / Misra, Rajeev (Co-author, Thesis director) / Mason, Hugh (Committee member) / Foy, Joseph (Committee member) / Biomedical Informatics Program (Contributor) / School of Life Sciences (Contributor) / W. P. Carey School of Business (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Mammary gland development in humans during puberty involves the enlargement of breast tissue, but this is not true in non-human primates. To identify potential causes of this difference, I examined variation in substitution rates across genes related to mammary development. Genes undergoing purifying selection show slower-than-average substitution rates, while genes undergoing positive selection show faster rates. These may be related to the difference between humans and other primates. Three genes were found to be accelerated were FOXF1, IGFBP5, and ATP2B2, but only the latter one was found in humans and it seems unlikely that it would be related to the differences between mammary gland development at puberty between humans and non-human primates.
ContributorsArroyo, Diana (Author) / Cartwright, Reed (Thesis director) / Wilson Sayres, Melissa (Committee member) / Schwartz, Rachel (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Alternative polyadenylation (APA) is the biological mechanism in which the same gene can have multiple 3'untranslated region (3'UTR) isoforms due to the presence of multiple polyadenylation signal (PAS) elements within the pre mRNAs. Because APA produces mRNA transcripts that have different 3'UTR isoforms, certain transcripts may be subject to post-transcriptional regulation by regulatory non-coding RNAs, such as microRNAs or RNA binding proteins defects of which have been implicated in diseases such as cancer. Despite the increasing level of information, functional understanding of the molecular mechanisms involved in transcription is still poorly understood, nor is it clear why APA is necessary at a cell or tissue-specific level. To address these questions I wanted to develop a set of sensor strain plasmids capable of detecting cleavage and polyadenylation in vivo, inject the complete sensor strain plasmid into C. elegans and prepare stable transgenic lines, and perform proof-of-principle RNAi feeding experiments targeting genes associated with the cleavage and polyadenylation complex machinery. I demonstrated that it was possible to create a plasmid capable of detecting cleavage and polyadenylation in C. elegans; however, issues arose during the RNAi assays indicating the sensor strain plasmid was not sensitive enough to the RNAi to effectively detect in the worms. Once the problems involved with sensitivity and variability in the RNAi effects are resolved, the plasmid would be able to better address questions regarding the functional understanding of molecular mechanisms involved in transcription termination.
ContributorsWilky, Henry Patrick (Author) / Mangone, Marco (Thesis director) / Newbern, Jason (Committee member) / Blazie, Stephen (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
The Dorrance Center for Rare Childhood Disorders is a unique research division at TGen (The Translational Genomics Research Institute) that provides personalized care to children and young adults facing rare, undiagnosed diseases. TGen scientists believe that the answers to these enigmatic disorders can often be found in a person's genetic code. They aim to solve these genetic mysteries using whole exome sequencing, a method that prioritizes the protein-coding portion of the genome in the search for disease-causing variants. Unfortunately, a communication gap sometimes exists between the TGen scientists and the patients they serve. I have seen, first hand, the kind of confusion that this study elicits in the families of its participants. Therefore, for my thesis, I decided to create a booklet that is meant to provide some clarity as to what exactly The Dorrance Center for Rare Childhood Disorders does to help diagnose children with rare disorders. The purpose of the booklet is to dispel any confusion regarding the study by providing a general review of genetics and an application of these lessons to the relevant sequencing technology as well as a discussion of the causes and effects of genetic mutations that often times are linked to rare childhood disorders.
ContributorsCambron, Julia Claire (Author) / LaBelle, Jeffrey (Thesis director) / Huentelman, Matt (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
There has been an alarming rise in the prevalence of obesity which has been attributed to the paralleled rise in consumption of high-fat foods. It’s commonly accepted that high-fat diets can lead to increased weight gain, however not all fats have the same physiological action. This study primarily focuses on the effect of canola oil, a monounsaturated fat, on energy homeostasis and body composition when it’s given as a supplement to a high-fat diet composed of saturated fatty acid. Rodent models were divided into three dietary groups: 1) low-fat diet (LFD), 2) high-fat diet (HFD) and 3) canola oils supplemented HFD (HF+CAN). After 4 weeks of dietary intervention, samples of epididymal fat, perinephric fat, and liver were analyzed across the three groups to see if the changes in energy homeostasis could be explained by the cellular behavior and composition of these tissues. Interestingly, the supplement of canola oil appeared to reverse the deleterious effects of a saturated fat diet, reverting energy intake, body weight gain and adipose tissue sizes to that (if not lower than that) of the LFD group. The only exception to this effect was the liver: the livers remained larger and fattier than those of the HFD. This occurrence is possibly due to a decrease in free fatty acid uptake in the adipose tissues—resulting in smaller adipose tissue sizes—and increased fatty acid uptake in the liver. The mechanism by which this occurs has yet to be elucidated and will be the primary focus of upcoming studies on the effect of monounsaturated fat on other diets.
ContributorsZuo, Connie Wanda (Author) / Washo-Krupps, Delon (Thesis director) / Deviche, Pierre (Committee member) / Herman, Richard (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
Western diets, high in dietary fat and red meat, are associated with hyperglycemia and weight gain, symptoms that promote insulin resistance and diabetes. Previous studies have shown that elevated glucose promotes glycation of circulating proteins such as albumin, which is thought to lead to hyperglycemia complications. It was hypothesized that diets with no meat consumption (pesco-vegetarian and lacto-vegetarian) would reduce protein glycation, in comparison to a diet with meat. Forty six healthy adult omnivorous subjects were randomized into one of three groups and instructed to either consume red meat (i.e. meat) or poultry twice per day (control), eliminate meat and increase fish consumption (pesco-vegetarian), or adopt a vegetarian diet devoid of fish, meat or poultry (lacto-vegetarian) for four weeks. Fasting plasma samples were collected from participants at baseline and after 4 weeks of the dietary intervention. Plasma glucose concentrations were measured using a commercially available kit. Percent glycated albumin was measured on a separate aliquot of plasma by mass spectrometry. Plasma glucose concentrations were significantly increased following 4-weeks of pesco-vegetarian diet (P=0.002, paired t-test). Neither the lacto-vegetarian (P=0.898) or the control diet (P=0.233) affected plasma glucose concentrations. Despite the significant increase in plasma glucose following a pesco-vegetarian diet, no change in percent glycated albumin was observed (P>0.50, ANOVA). These findings may indicate a protective effect of the pesco-vegetarian diet on protein glycation in the presence of elevated plasma glucose and suggest the need for additional studies to examine the link between increased fish consumption and glucose regulation.
ContributorsRaad, Noor (Author) / Sweazea, Karen (Thesis director, Committee member) / Borges, Chad (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
Birds have unusually high plasma glucose concentrations compared to mammals of similar size despite their high metabolic rate. While birds use lipids as their main source of energy, it is still unclear how and why they maintain high plasma glucose concentrations. To investigate a potential underlying mechanism, this study looks at the role of lipolysis in glucose homeostasis. The purpose of this study is to examine the effects of decreased glycerol availability (through inhibition of lipolysis) on plasma glucose concentrations in mourning doves. The hypothesis is that decreased availability of glycerol will result in decreased production of glucose through gluconeogenesis leading to reduced plasma glucose concentrations. In the morning of each experiment, mourning doves were collected at the Arizona State University Tempe campus, and randomized into either a control group (0.9% saline) or experimental group (acipimox, 50mg/kg BM). Blood samples were collected prior to treatment, and at 1, 2, and 3 hours post-treatment. At 3 hours, doves were euthanized, and tissue samples were collected for analysis. Acipimox treatment resulted in significant increases in blood glucose concentrations at 1 and 2 hours post- treatment as well as renal triglyceride concentrations at 3 hours post-treatment. Change in plasma free glycerol between 0h and 3h followed an increasing trend for the acipimox treated animals, and a decreasing trend in the saline treated animals. These results do not support the hypothesis that inhibition of lipolysis should decrease blood glycerol and blood glucose levels. Rather, the effects of acipimox in glucose homeostasis appear to differ significantly between birds and mammals suggesting differing mechanisms for glucose homeostasis.
ContributorsKouteib, Soukaina (Author) / Sweazea, Karen (Thesis director) / Deviche, Pierre (Committee member) / Chandler, Douglas (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
Schizophrenia affects 1.1% of the population worldwide. Schizophrenia is a complex, multifactorial disorder. Stress can trigger psychotic episodes and exacerbate schizophrenic symptoms. For humans, one gene implicated in stress and schizophrenia in humans is the early growth response 3 (EGR3). Patients with genomic variations in EGR3 have reduced levels of EGR3 in the prefrontal brain region compared with healthy patients. Schizophrenic patients also have less serotonin 2A receptor (5HT2AR), which is coded by the gene Htr2a, in their prefrontal cortex. Mice that are Egr3-deficient also have decreased levels of 5HT2AR, suggesting that Egr3 may be involved in the regulation of 5HT2AR. The purpose of the experiment is to determine if EGR3 binds to the Htr2a gene promoter region by using a Chromatin immunoprecipitation (ChIP) assay. We will use ECS to increase EGR3 expression. Previously we have identified two upstream sites of interest where EGR3 potentially binds to the Htr2a gene, one which is distal and one proximal to the transcription start site. After ECS, increased binding is seen in the Htr2a distal region with EGR3 via the ChIP assay. Increased binding was not observed at either of the promoter sites; however, the t-test comparing the distal site of the ECS and the No ECS groups to have a p-value of 0.056, suggesting that increasing the number of animals (n=7) could possibly give a more accurate representation to test our hypothesis. However, the experiment still suggests increased expression and that EGR3 may bind to the distal site of Htr2a. Keywords: stress, environment, genetics, schizophrenia, EGR3, chromatin immunoprecipitation
ContributorsMishra, Abhinav (Author) / Buetow, Kenneth (Thesis director) / Gallitano, Amelia (Committee member) / Zhao, Xiuli (Committee member) / Barrett, The Honors College (Contributor) / School of Politics and Global Studies (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
With the rising prevalence of obesity and diabetes, novel treatments to help mitigate or prevent symptoms of these conditions are warranted. Prior studies have shown that fossilized plant materials found in soil lowers blood sugar in a mouse model of diabetes. The goal of this study is to determine whether a similar organometallic complex (OMC) could prevent insulin resistance in the skeletal muscle brought on by chronic high fat intake by examining the protein expression of key enzymes in the insulin signaling pathway and examining glucoregulatory measures. Six-week-old periadolescent male Sprague-Dawley rats (n=42) were randomly chosen to be fed either a high fat diet (HFD) (20% protein, 20% carbohydrates [6.8% sucrose], 60% fat) or a standard chow diet (18.9% protein, 57.33% carbohydrates, 5% fat) for 10 weeks. Rats from each diet group were then randomly assigned to one of three doses of OMC (0, 0.6, 3.0 mg/mL), which was added to their drinking water and fasting blood glucose was measured at baseline and again at 10 weeks. After 10 weeks, rats were euthanized, and soleus muscle samples were isolated, snap-frozen, and stored at -80°C until analyses. Fasting plasma glucose was measured using a commercially available glucose oxidase kit. Following 6 and 10 weeks, HFD rats developed significant hyperglycemia (p<0.001 and p=0.025) compared to chow controls which was prevented by high dose OMC (p=0.021). After 10 weeks, there were significant differences in fasting serum insulin between diets (p=0.009) where levels were higher in HFD rats. No significant difference was seen in p-PI3K expression between groups. These results suggest that OMC could prevent insulin resistance by reducing hyperglycemia. Further studies are needed to characterize the effects of diet and OMC on the insulin signaling pathway in skeletal muscle, the main site of postprandial glucose disposal. This study was supported by a grant from Isagenix International LLC as well as funds from Barrett, the Honors College at Arizona State University, Tempe Campus.
ContributorsStarr, Ashlee (Author) / Sweazea, Karen (Thesis director) / Johnston, Carol (Committee member) / Hyatt, JP (Committee member) / Sanford School of Social and Family Dynamics (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12