Matching Items (77)
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This dissertation research project developed as an urgent response to physical inactivity, which has resulted in increased rates of obesity, diabetes, and metabolic disease worldwide. Incorporating enough daily physical activity (PA) is challenging for most people. This research aims to modulate the brain's reward systems to increase motivation for PA

This dissertation research project developed as an urgent response to physical inactivity, which has resulted in increased rates of obesity, diabetes, and metabolic disease worldwide. Incorporating enough daily physical activity (PA) is challenging for most people. This research aims to modulate the brain's reward systems to increase motivation for PA and, thus, slow the rapid increase in sedentary lifestyles. Transcranial direct current stimulation (tDCS) involves brain neuromodulation by facilitating or inhibiting spontaneous neural activity. tDCS applied to the dorsolateral prefrontal cortex (DLPFC) increases dopamine release in the striatum, an area of the brain involved in the reward–motivation pathways. I propose that a repeated intervention, consisting of tDCS applied to the DLPFC followed by a short walking exercise stimulus, enhances motivation for PA and daily PA levels in healthy adults. Results showed that using tDCS followed by short-duration walking exercise may enhance daily PA levels in low-physically active participants but may not have similar effects on those with higher levels of daily PA. Moreover, there was a significant effect on increasing intrinsic motivation for PA in males, but there were no sex-related differences in PA. These effects were not observed during a 2-week follow-up period of the study after the intervention was discontinued. Further research is needed to confirm and continue exploring the effects of tDCS on motivation for PA in larger cohorts of sedentary populations. This novel research will lead to a cascade of new evidence-based technological applications that increase PA by employing approaches rooted in biology.
ContributorsRuiz Tejada, Anaissa (Author) / Katsanos, Christos (Thesis advisor) / Neisewander, Janet (Committee member) / Sadleir, Rosalind (Committee member) / Buman, Matthew (Committee member) / Arizona State University (Publisher)
Created2023
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Advancements in high-throughput biotechnologies have generated large-scale multi-omics datasets encompassing diverse dimensions such as genomics, epigenomics, transcriptomics, proteomics, metabolomics, metagenomics, and phenomics. Traditionally, statistical and machine learning-based approaches utilize single-omics data sources to uncover molecular signatures, dissect complicated cellular mechanisms, and predict clinical results. However, to capture the multifaceted pathological

Advancements in high-throughput biotechnologies have generated large-scale multi-omics datasets encompassing diverse dimensions such as genomics, epigenomics, transcriptomics, proteomics, metabolomics, metagenomics, and phenomics. Traditionally, statistical and machine learning-based approaches utilize single-omics data sources to uncover molecular signatures, dissect complicated cellular mechanisms, and predict clinical results. However, to capture the multifaceted pathological mechanisms, integrative multi-omics analysis is needed that can provide a comprehensive picture of the disease. Here, I present three novel approaches to multi-omics integrative analysis. I introduce a single-cell integrative clustering method, which leverages multi-omics to enhance the resolution of cell subpopulations. Applied to a Cellular Indexing of Transcriptomes and Epitopes (CITE-Seq) dataset from human Acute Myeloid Lymphoma (AML) and control samples, this approach unveiled nuanced cell populations that otherwise remain elusive. I then shift the focus to a computational framework to discover transcriptional regulatory trios in which a transcription factor binds to a regulatory element harboring a genetic variant and subsequently differentially regulates the transcription level of a target gene. Applied to whole-exome, whole-genome, and transcriptome data of multiple myeloma samples, this approach discovered synergetic cis-acting and trans-acting regulatory elements associated with tumorigenesis. The next part of this work introduces a novel methodology that leverages the transcriptome and surface protein data at the single-cell level produced by CITE-Seq to model the intracellular protein trafficking process. Applied to COVID-19 samples, this approach revealed dysregulated protein trafficking associated with the severity of the infection.
ContributorsMudappathi, Rekha (Author) / Liu, Li (Thesis advisor) / Dinu, Valentin (Committee member) / Sun, Zhifu (Committee member) / Arizona State University (Publisher)
Created2023
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Innate immunity is regulated at both the transcriptional and epigenetic level. However, the complex epigenetic regulation of inflammatory responses in innate immunity remains to be fully characterized. The objective was to characterize the function of a NAD+-dependent lysine deacetylase SIRT7 in regulating polarization and inflammatory responses in bone marrow derived

Innate immunity is regulated at both the transcriptional and epigenetic level. However, the complex epigenetic regulation of inflammatory responses in innate immunity remains to be fully characterized. The objective was to characterize the function of a NAD+-dependent lysine deacetylase SIRT7 in regulating polarization and inflammatory responses in bone marrow derived macrophages. In primary bone marrow derived macrophages, LPS induced significant pro-inflammatory responses. LysM-Cre induced SIRT7 knockout (KO) male macrophages exhibited enhanced inflammatory responses compared to WT macrophages. Interestingly, we did not observe a similar trend in female cells. In fact, loss of SIRT7 in female macrophages induced weaker proinflammatory responses when challenged with LPS. As an epigenetic co-factor, SIRT7 is known to interact with multiple inflammation related nuclear hormone receptors, such as glucocorticoid receptor (GR), and vitamin D receptor (VDR). Therefore, we examined whether the glucocorticoid or vitamin D induced anti-inflammatory responses are affected in SIRT7 KO macrophages. Preliminary results suggest that both glucocorticoid and vitamin D are still able to inhibit LPS-induced inflammatory responses in SIRT7 KO cells. Future studies using RNA-seq and epigenetic assays will be needed to determine the sex-specific function of SIRT7 in macrophage activation. 
ContributorsMikkilineni, Sneha (Author) / Katsanos, Christos (Thesis director) / Wei, Zong (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2022-05
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Description

According to the CDC, obesity has increased from 30.5% to 42.4% over the past 18 years. Western diets (WDs) consist of large portions in high fats, high carbohydrates, excess sugar and high-glycemic foods that can cause metabolic complications and mitochondrial dysfunction. Diet-induced obesity can lead to changes in muscle metabolism

According to the CDC, obesity has increased from 30.5% to 42.4% over the past 18 years. Western diets (WDs) consist of large portions in high fats, high carbohydrates, excess sugar and high-glycemic foods that can cause metabolic complications and mitochondrial dysfunction. Diet-induced obesity can lead to changes in muscle metabolism and muscle fiber phenotypes, which in turn lead to metabolic complications. Muscle fiber phenotype is determined protein isoform-content of myosin heavy chain (MHC). Regular exercise alters mitochondrial content and fat oxidation and shifts MHC proportions under healthy circumstances. However, diet and exercise-driven fiber type shifts in diet-induced obesity are less understood. We designed our experiment to better understand the impact of diet and/ or exercise on fiber type content of gastrocnemius muscle in diet-induced obese mice. Exercise and genistein may be used as a treatment strategy to restore the MHC proportions in obese subjects to that of the lean subjects. We hypothesized that genistein and exercise would have the greatest MHC I change in muscle fiber phenotype of mouse gastrocnemius muscles. Further, we also hypothesized that a standard diet would reverse the expected increase in fast fiber phenotype (MHC IIb). Lastly, we also hypothesized that exercise would also reduce the abundance of MHC IIb. Gastrocnemius muscles were collected from mice, homogenized, run through gel electrophoresis and stained to give muscle fiber proportions. Paired sample t-tests were conducted for differences between the MHC isoforms compared to the lean (LN) and high-fat diet (HFD) control groups. The results showed that genistein and exercise significantly increased the abundance of MHC I muscle fibers (19%, p<0.05). Additionally, diet and exercise restored the muscle fiber phenotype to that of lean control. As expected, HFD obese mice exhibited elevated fast twitch fibers compared to only 3% slow twitch fibers. These findings show the potential for exercise and supplementation of genistein as a strategy to combat diet induced obesity. Future research should aim to understand the mechanisms that genistein acts on to make these changes, and aim to replicate these data in humans with obesity.

ContributorsSodhi, Harkaran (Author) / Katsanos, Christos (Thesis director) / Wang, Shu (Committee member) / Serrano, Nathan (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2022-05
Description
Obesity is a complex metabolic condition characterized by excessive adipose tissue accumulation, often leading to adverse health outcomes such as insulin resistance, cardiovascular disease, and reduced physical function. This paper delves into the dynamic spectrum of muscle fiber types in obesity, highlighting their continuum nature rather than rigid classifications. We

Obesity is a complex metabolic condition characterized by excessive adipose tissue accumulation, often leading to adverse health outcomes such as insulin resistance, cardiovascular disease, and reduced physical function. This paper delves into the dynamic spectrum of muscle fiber types in obesity, highlighting their continuum nature rather than rigid classifications. We explore how alterations in fiber distribution, particularly an increase in hybrid fibers and glycolytic types, are more prevalent in obese individuals.
ContributorsWright, Makenzi (Author) / Katsanos, Christos (Thesis director) / Serrano, Nathan (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2024-05
Description
A genome wide association study (GWAS) of treatment outcomes for citalopram and escitalopram, two frontline SSRI treatments for Major Depressive Disorder, was conducted with 529 subjects on an imputed dataset. While no variants of genome-wide significance were identified, various potentially interesting variants were identified that warrant further exploration. These findings

A genome wide association study (GWAS) of treatment outcomes for citalopram and escitalopram, two frontline SSRI treatments for Major Depressive Disorder, was conducted with 529 subjects on an imputed dataset. While no variants of genome-wide significance were identified, various potentially interesting variants were identified that warrant further exploration. These findings have the potential to elucidate novel mechanisms underlying drug response for SSRIs. This work will be continued further, with machine learning and deep learning analyses to perform non-linear analyses and employing a biologist or geneticist to provide more specialized knowledge for interpretation of results.
ContributorsLeiter-Weintraub, Ethan (Author) / Dinu, Valentin (Thesis director) / Scotch, Matthew (Committee member) / Barrett, The Honors College (Contributor) / Dean, W.P. Carey School of Business (Contributor) / College of Health Solutions (Contributor) / School of Life Sciences (Contributor)
Created2024-05
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In this quantitative research paper, we explored the correlation between the six dimensions of motivation as part of the Self-Determination Theory spectrum and physical activity. In addition, our aim was to also see if Transcranial Direct Current Stimulation (tDCS) paired with exercise as an intervention would affect motivation to exercise

In this quantitative research paper, we explored the correlation between the six dimensions of motivation as part of the Self-Determination Theory spectrum and physical activity. In addition, our aim was to also see if Transcranial Direct Current Stimulation (tDCS) paired with exercise as an intervention would affect motivation to exercise over time.

ContributorsPankoff, Mia (Author) / Quezada, Gabrielle (Co-author) / Katsanos, Christos (Thesis director) / Shaffer, Zachary (Committee member) / Ruiz Tejada, Anaissa (Committee member) / Barrett, The Honors College (Contributor) / Edson College of Nursing and Health Innovation (Contributor)
Created2021-12
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Description

In this quantitative research paper, we explored the correlation between the six dimensions of motivation as part of the Self-Determination Theory spectrum and physical activity. In addition, our aim was to also see if Transcranial Direct Current Stimulation (tDCS) paired with exercise as an intervention would affect motivation to exercise

In this quantitative research paper, we explored the correlation between the six dimensions of motivation as part of the Self-Determination Theory spectrum and physical activity. In addition, our aim was to also see if Transcranial Direct Current Stimulation (tDCS) paired with exercise as an intervention would affect motivation to exercise over time.

ContributorsQuezada, Gabrielle (Author) / Pankoff, Mia (Co-author) / Katsanos, Christos (Thesis director) / Shaffer, Zachary (Committee member) / Ruiz Tejada, Anaissa (Committee member) / Barrett, The Honors College (Contributor) / Edson College of Nursing and Health Innovation (Contributor) / College of Integrative Sciences and Arts (Contributor)
Created2021-12
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Description
Vitamin D is a nutrient that is obtained through the diet and vitamin D supplementation and created from exposure to Ultraviolet B (UVB) radiation. While there are many factors that determine how much serum 25-hydroxyvitamin D (25(OH)D) concentration is in the body, little is known about how genetic variation in

Vitamin D is a nutrient that is obtained through the diet and vitamin D supplementation and created from exposure to Ultraviolet B (UVB) radiation. While there are many factors that determine how much serum 25-hydroxyvitamin D (25(OH)D) concentration is in the body, little is known about how genetic variation in vitamin D-related genes influences serum 25(OH)D concentrations resulting from daily vitamin D intake and exposure to direct sunlight. Previous studies show that common genetic variants rs10741657 (CYP2R1), rs4588 (GC), rs228678 (GC), and rs4516035 (VDR) act as moderators and alter the effect of outdoor time and vitamin D intake on serum 25(OH)D concentrations. The objective of this study is to analyze the associations between serum 25(OH)D concentrations resulting from outdoor time and vitamin D intake, and genetic risk scores (GRS) established from previous studies involving single nucleotide polymorphisms (SNP) located on or near genes involving vitamin D synthesis, transport, activation, and degradation in 102 Hispanic and Non-Hispanic adults in the San Diego County, California. This study is a secondary analysis of data from the Community of Mine study. Global Positioning System (GPS) data collected by the Qstarz GPS device worn by each participant was used to measure outdoor time, a proxy measurement for sun exposure time. Vitamin D intake was assessed using two 24-hour dietary recalls. Blood samples were measured for serum 25(OH)D concentrations. DNA was provided to assess each participant for the various genetic variants. Adjusted analyses of the GRS and serum 25(OH)D concentrations showed that individuals with high GRS (3-4) had lower serum 25(OH)D concentrations than individuals with low GRS (0-2) for both Nissen GRS and Rivera-Paredez GRS.
ContributorsAnderson, Heather Ray (Author) / Sears, Dorothy (Thesis advisor) / Alexon, Christy (Committee member) / Dinu, Valentin (Committee member) / Jankowska, Marta (Committee member) / Arizona State University (Publisher)
Created2022
Description

In light of recent school-policy movements that encourage recess be moved before lunch, the present study seeks to examine the relationship between food consumption and immediate, subsequent physical activity (PA) and, more specifically, if a risk would be posed to the amount of children's PA if food is not consumed

In light of recent school-policy movements that encourage recess be moved before lunch, the present study seeks to examine the relationship between food consumption and immediate, subsequent physical activity (PA) and, more specifically, if a risk would be posed to the amount of children's PA if food is not consumed directly before activity. A cross-section study was performed measuring (a) lunch composition (in terms of food groups defined by the USDA's food plate), (b) lunch consumption, and (c) moderate-to-vigorous physical activity (MVPA) during the following recess period, in consenting third through sixth grade students. The relationship between food consumption and percentage of recess time spent in MVPA was determined to be weak. However, the study identified low average provision and consumption rates across all food groups and evaluated this through the lease of current school lunch policy/formatting.

ContributorsWolfe, Ariana (Author) / Poulos, Allison (Thesis director) / Katsanos, Christos (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2023-05