Matching Items (8)
Description
Lipid membranes are a key structure for many classes of viruses. Lipid membranes can be analyzed using the fluid mosaic model, which states that the phospholipid membrane has variable amounts of fluidity and key membrane proteins are presented in areas stabilized by cholesterol-enriched platforms called lipid rafts. This project aims to further the understanding of the importance of lipid rafts in measles virus (MV) infection and replication, which has not been extensively studied. In order to do this, an MV-susceptible cell line was treated with an anti-cholesterol compound before and after measles virus infection. I found that pre-infection treatments had a marginal effect upon measles cytopathic effect (syncytia formation) or replication. Twenty-four hours post-infection treatment had a deleterious effect on cell viability, but the replication/assembly of infectious units per cell decreased importantly and in dose-dependent manner. Furthermore, by measuring the susceptibility to neutralization of infectious particles obtained from MBCD treated cells, I determined the importance of lipid microdomain environment on the stability of infectious particles. Increased anti-cholesterol treatment enhanced the susceptibility of MV to neutralization. Future studies are proposed to assess the properties of cholesterol depleted viral infectious units.
ContributorsYkema, Matthew Ryan (Author) / Mor, Tsafrir (Thesis director) / Jacobs, Bertram (Committee member) / Julik, Emily (Committee member) / Barrett, The Honors College (Contributor) / Economics Program in CLAS (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
Turmeric is the bright yellow root that has been used as a spice, healing remedy, and textile dye. Previous studies have suggested that the most active ingredient in turmeric, curcumin, could reduce serum cholesterol concentration. However, most of these studies were conducted on animals and not many have been done on controlled human trials. This randomized, double-blinded, controlled crossover study evaluates the effects of turmeric on blood cholesterol concentrations including total cholesterol, LDL cholesterol, HLD cholesterol, and triglycerides. In this study, eight healthy participants between the ages of 18 and 45 were randomized to receive either 500mg capsules of turmeric or placebo for a period of three weeks. Following a wash-out period of five weeks, all participants were crossed over to the alternative treatment for another three weeks. After comparing the 3 week treatment and placebo phases, turmeric showed no significant effect on serum lipid concentrations. Furthermore, a slight increase in total cholesterol concentrations was observed following the turmeric phase when compared to the placebo phase.
ContributorsDo, Ngoc Bich Thi (Author) / Johnston, Carol (Thesis director) / Whisner, Corrie (Committee member) / School of Nutrition and Health Promotion (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Cardiovascular disease attributed to about 800,000 deaths per year and is the leading cause of all-cause mortality in the U.S. Previous studies indicate that reducing sedentary time or increasing physical activity (PA) can independently reduce cardiometabolic risk (CMR). Further, studies have shown that higher levels of moderate-to-vigorous PA can attenuate the negative effects of sedentary behavior on CMR.
In this study, we evaluated the association between sedentary time, light-intensity PA (LPA), and moderate-vigorous PA (MVPA) and CMR biomarkers (high density lipoprotein level, low density lipoprotein level, triglycerides, fasting glucose, total cholesterol, blood pressure, and body mass index). Additionally, we examined if the detrimental association between sedentary time and CMR biomarkers is partially or fully attenuated by MVPA. Baseline objective physical activity and cardiometabolic risk data from a two-arm-cluster randomized trial (Stand&Move@work) were used in this study. Multilevel models clustered by worksite evaluated the fixed effects and interaction between MVPA and sedentary time on CMR. Data from 630 sedentary working adults (from 24 worksites) were included in the analysis. The sample was mainly middle aged (44.6±11.2) females (74%) with race distributions as follows; 70.5% white, 13.8% hispanic, 4.1% black, 5.1% asian, and 2.1% other. Our study showed detrimental trends consistent with previous studies between sedentary behavior and cardiometabolic outcomes including HDL, LDL, and total cholesterol. MVPA demonstrated beneficial associations with lipoproteins including HDL, LDL, total cholesterol, and triglycerides. We observed that high levels of MVPA may be able to partially attenuate the negative effects of highly sedentary behavior on fasting glucose, total cholesterol, and LDL levels. Overall, sedentary behavior indicated deleterious associations with cardiometabolic outcomes. Future directions for this study could examine a more at-risk population or a highly active population for further assessment of CMR biomarkers and the effects of behavior.
In this study, we evaluated the association between sedentary time, light-intensity PA (LPA), and moderate-vigorous PA (MVPA) and CMR biomarkers (high density lipoprotein level, low density lipoprotein level, triglycerides, fasting glucose, total cholesterol, blood pressure, and body mass index). Additionally, we examined if the detrimental association between sedentary time and CMR biomarkers is partially or fully attenuated by MVPA. Baseline objective physical activity and cardiometabolic risk data from a two-arm-cluster randomized trial (Stand&Move@work) were used in this study. Multilevel models clustered by worksite evaluated the fixed effects and interaction between MVPA and sedentary time on CMR. Data from 630 sedentary working adults (from 24 worksites) were included in the analysis. The sample was mainly middle aged (44.6±11.2) females (74%) with race distributions as follows; 70.5% white, 13.8% hispanic, 4.1% black, 5.1% asian, and 2.1% other. Our study showed detrimental trends consistent with previous studies between sedentary behavior and cardiometabolic outcomes including HDL, LDL, and total cholesterol. MVPA demonstrated beneficial associations with lipoproteins including HDL, LDL, total cholesterol, and triglycerides. We observed that high levels of MVPA may be able to partially attenuate the negative effects of highly sedentary behavior on fasting glucose, total cholesterol, and LDL levels. Overall, sedentary behavior indicated deleterious associations with cardiometabolic outcomes. Future directions for this study could examine a more at-risk population or a highly active population for further assessment of CMR biomarkers and the effects of behavior.
ContributorsMeyer, Emily Camille (Author) / Buman, Matthew (Thesis director) / Toledo, Meynard (Committee member) / Pereira, Mark (Committee member) / School of Life Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
There are limited studies exploring the direct relationship between coconut oil and cholesterol concentrations. Research in animals and a few intervention trials suggest that coconut oil increases the good cholesterol (high density lipoprotein, HDL) and thus reduces the risk of cardiovascular disease. Preliminary research at Arizona State University (ASU) has found similar results using coconut oil as a placebo, positive changes in HDL cholesterol concentrations were observed.
The goal of this randomized, double blind, parallel two arm study, was to further examine the beneficial effects of a 2g supplement of coconut oil taken each day for 8 weeks on cholesterol concentrations, specifically the total cholesterol to HDL cholesterol ratio, compared to placebo.
Forty-two healthy adults between 18-40 years of age, exercising less than 150 minutes each week, non smoking, BMI between 22-35 and not taking any medications that could effect blood lipids were recruited from the ListServs at ASU. Participants were randomized to receive either a placebo capsule of flour or a coconut oil capsule (Puritan’s Pride brand, coconut oil softgels, 2g each) and instructed to take the capsules for 8 weeks.
Results indicated no significant change in total cholesterol to HDL ratio between baseline and 8 weeks in the coconut oil and placebo groups (p=0.369), no significant change in HDL (p=0.648), no change in LDL (p=0.247), no change in total cholesterol (p=0.216), and no change in triglycerides (p=0.369).
Blood lipid concentrations were not significantly altered by a 2g/day dosage of coconut oil over the course of 8 weeks in healthy adults, and specifically the total cholesterol to HDL ratio did not change or improve.
The goal of this randomized, double blind, parallel two arm study, was to further examine the beneficial effects of a 2g supplement of coconut oil taken each day for 8 weeks on cholesterol concentrations, specifically the total cholesterol to HDL cholesterol ratio, compared to placebo.
Forty-two healthy adults between 18-40 years of age, exercising less than 150 minutes each week, non smoking, BMI between 22-35 and not taking any medications that could effect blood lipids were recruited from the ListServs at ASU. Participants were randomized to receive either a placebo capsule of flour or a coconut oil capsule (Puritan’s Pride brand, coconut oil softgels, 2g each) and instructed to take the capsules for 8 weeks.
Results indicated no significant change in total cholesterol to HDL ratio between baseline and 8 weeks in the coconut oil and placebo groups (p=0.369), no significant change in HDL (p=0.648), no change in LDL (p=0.247), no change in total cholesterol (p=0.216), and no change in triglycerides (p=0.369).
Blood lipid concentrations were not significantly altered by a 2g/day dosage of coconut oil over the course of 8 weeks in healthy adults, and specifically the total cholesterol to HDL ratio did not change or improve.
ContributorsShedden, Rachel (Author) / Johnston, Carol (Thesis advisor) / Lespron, Christy (Committee member) / Shepard, Christina (Committee member) / Arizona State University (Publisher)
Created2017
Description
Lipid microdomains play a vital role in a number of biological processes. They are often a target of diseases and viruses. Viruses in particular utilize lipid microdomains to gain entry and fuse with the host-cell membrane. Measles virus (MV) a human pathogen, spread from cell to cell by inducing fusion of cellular membranes. This causes the formation of large multinucleated cells, syncytia. It has been previously reported that lipid microdomains are essential for measles virus infection/replication. In this study we used methyl beta cyclodextrin (MBCD), a cholesterol-sequestering agent to disrupt lipid microdomains. Through transfection of Vero h/SLAM cells, we found that Measles virus fusion was dependent on lipid microdomains integrity. Indeed, a dose dependent fusion inhibition was documented with increasing concentrations of MBCD resulting in reduced formation of syncytia.
ContributorsKwan, Jason (Author) / Reyes del Valle, Jorge (Thesis director) / Chang, Yung (Committee member) / Mor, Tsafrir (Committee member) / Barrett, The Honors College (Contributor) / Department of Finance (Contributor) / School of Life Sciences (Contributor)
Created2013-05
Description
My research examines the case of Joseph Vacher, one of the most prolific serial murderers in French history, as a micro- historical study to analyze the evolution of criminal theory and application of the insanity defense over the course of the Belle Époque, as French judicial systems and medico-legal experts attempted to cope with the emerging psychiatric distinction between mental illness and personality disorders. Historically, attempts to explain seemingly unmotivated homicides left a narrow margain for mitigating factors, aside from pleas of insanity. The success of such pleas reflected the conviction that these crimes could only result from severe mental incapacity. Nevertheless, in the late nineteenth century, there emerged a new medical perspective, the sadism diagnosis. Those involved in the realm of criminal behavior began to entertain the possibility that certain individuals might commit violent acts in pursuit of pleasure while maintaining full command of their reason.
ContributorsKlosterman, Isabel Maria (Author) / Fuchs, Rachel (Thesis director) / Wright, Kent (Committee member) / Hopkins, Richard (Committee member) / Barrett, The Honors College (Contributor) / School of Historical, Philosophical and Religious Studies (Contributor) / School of Politics and Global Studies (Contributor)
Created2013-05
Description
High fiber diets have been associated with improved cardiometabolic health with specific efforts to lower circulating levels of low-density lipoprotein (LDL cholesterol). Whole grain and grain-based foods are major contributors of dietary fiber in the American diet, of which wheat has been extensively studied. Corn, however, has not been well studied for its cholesterol-lowering properties. Further, the mechanisms by which grains improve cardiometabolic health require further exploration with regard to the human microbiome. The objective of this single-blind randomized controlled, crossover trial was to assess the impact of three different corn flours (whole grain, refined, and bran-enhanced refined flour mixture) on serum LDL cholesterol and the gut microbiota diversity and composition. Twenty-three participants were recruited, between the ages of 18-70 with hypercholesterolemia (Male = 10, Female = 13, LDL >120 mg/dL) who were not taking any cholesterol-lowering medications. Participants consumed each flour mixture for 4 weeks prepared as muffins and pita breads. At the beginning and end of each 4-week period serum for cholesterol assessment, anthropometrics, and stool samples were obtained. Serum cholesterol was assessed using a clinical analyzer. Stool samples were processed, and microbial DNA extracted and sequenced based on the 16S rRNA gene. A generalized linear model demonstrated a significant treatment effect (p=0.016) on LDL cholesterol and explained a majority of the variance (R-squared= 0.89). Post hoc tests revealed bran-enhanced refined flour had a significant effect on cholesterol in comparison to whole grain flour (p=0.001). No statistically significant differences were observed for gut microbial community composition (Jaccard and weighted Unifrac) after corn consumption. However, relative abundance analysis (LEfSE) identified Mycobacterium celatum (p=0.048 FDR=0.975) as a potential marker of post-corn consumption with this microbe being differentially less abundant following bran-enhanced flour treatment. These data suggest that corn flour consumption may be beneficial for individuals with hypercholesterolemia but the role of gut microbiota in this relationship requires further exploration, especially given the small sample size. Further research and analysis of a fully powered cohort is needed to more accurately describe the associations and potential mechanisms of corn-derived dietary fiber on circulating LDL cholesterol and the gut microbiota.
ContributorsWilson, Shannon L (Author) / Whisner, Corrie M (Thesis advisor) / Sears, Dorothy (Committee member) / Buman, Matthew (Committee member) / Dickinson, Jared (Committee member) / Zhu, Qiyun (Committee member) / Arizona State University (Publisher)
Created2022
Description
G protein-coupled receptors (GPCRs) are known to be modulated by membrane cholesterol levels, but whether or not the effects are caused by specific receptor-cholesterol interactions or cholesterol’s general effects on the membrane is not well-understood. Results from coarse-grained molecular dynamics (CGMD) simulations coupled and structural bioinformatics offer new insights into how cholesterol modulates GPCR function by showing cholesterol interactions with β2AR that agree with previously published data. Additionally, differential and specific cholesterol binding in the CCK receptor subfamily was observed while revealing a previously unreported Cholesterol Recognition Amino-acid Consensus (CRAC) sequence that is also conserved across 38% of class A GPCRs. Mutation of this conserved CRAC sequence of the β2AR affects cholesterol stabilization of the receptor in a lipid bilayer. Serial femtosecond crystallography (SFX) with X-ray free electron lasers (XFELs) has proven highly successful for structure determination of challenging membrane proteins crystallized in lipidic cubic phase, however, as most techniques, it has limitations. Using an optimized SFX experimental setup in a helium atmosphere we determined the room temperature structure of the adenosine A2A receptor (A2AAR) at 2.0 Å resolution and compared it with previous A2AAR structures determined in vacuum and/or at cryogenic temperatures. Specifically, we demonstrated the capability of utilizing high XFEL beam transmissions, in conjunction with a high dynamic range detector, to collect high-resolution SFX data while reducing crystalline material consumption and shortening the collection time required for a complete data set.
The results of these studies provide a better understanding of receptor-cholesterol interactions that can contribute to novel and improved therapeutics for a variety of diseases. Furthermore, the experimental setups presented herein can be applied to future molecular dynamics and SFX applications for protein nanocrystal samples to aid in structure-based discovery efforts of therapeutic targets that are difficult to crystallize.
The results of these studies provide a better understanding of receptor-cholesterol interactions that can contribute to novel and improved therapeutics for a variety of diseases. Furthermore, the experimental setups presented herein can be applied to future molecular dynamics and SFX applications for protein nanocrystal samples to aid in structure-based discovery efforts of therapeutic targets that are difficult to crystallize.
ContributorsGeiger, James (Author) / Liu, Wei (Thesis advisor) / Mills, Jeremy (Committee member) / Chiu, Po-Lin (Committee member) / Arizona State University (Publisher)
Created2020