Matching Items (555)
Description
Rewired biological pathways and/or rewired microRNA (miRNA)-mRNA interactions might also influence the activity of biological pathways. Here, rewired biological pathways is defined as differential (rewiring) effect of genes on the topology of biological pathways between controls and cases. Similarly, rewired miRNA-mRNA interactions are defined as the differential (rewiring) effects of miRNAs on the topology of biological pathways between controls and cases. In the dissertation, it is discussed that how rewired biological pathways (Chapter 1) and/or rewired miRNA-mRNA interactions (Chapter 2) aberrantly influence the activity of biological pathways and their association with disease.
This dissertation proposes two PageRank-based analytical methods, Pathways of Topological Rank Analysis (PoTRA) and miR2Pathway, discussed in Chapter 1 and Chapter 2, respectively. PoTRA focuses on detecting pathways with an altered number of hub genes in corresponding pathways between two phenotypes. The basis for PoTRA is that the loss of connectivity is a common topological trait of cancer networks, as well as the prior knowledge that a normal biological network is a scale-free network whose degree distribution follows a power law where a small number of nodes are hubs and a large number of nodes are non-hubs. However, from normal to cancer, the process of the network losing connectivity might be the process of disrupting the scale-free structure of the network, namely, the number of hub genes might be altered in cancer compared to that in normal samples. Hence, it is hypothesized that if the number of hub genes is different in a pathway between normal and cancer, this pathway might be involved in cancer. MiR2Pathway focuses on quantifying the differential effects of miRNAs on the activity of a biological pathway when miRNA-mRNA connections are altered from normal to disease and rank disease risk of rewired miRNA-mediated biological pathways. This dissertation explores how rewired gene-gene interactions and rewired miRNA-mRNA interactions lead to aberrant activity of biological pathways, and rank pathways for their disease risk. The two methods proposed here can be used to complement existing genomics analysis methods to facilitate the study of biological mechanisms behind disease at the systems-level.
This dissertation proposes two PageRank-based analytical methods, Pathways of Topological Rank Analysis (PoTRA) and miR2Pathway, discussed in Chapter 1 and Chapter 2, respectively. PoTRA focuses on detecting pathways with an altered number of hub genes in corresponding pathways between two phenotypes. The basis for PoTRA is that the loss of connectivity is a common topological trait of cancer networks, as well as the prior knowledge that a normal biological network is a scale-free network whose degree distribution follows a power law where a small number of nodes are hubs and a large number of nodes are non-hubs. However, from normal to cancer, the process of the network losing connectivity might be the process of disrupting the scale-free structure of the network, namely, the number of hub genes might be altered in cancer compared to that in normal samples. Hence, it is hypothesized that if the number of hub genes is different in a pathway between normal and cancer, this pathway might be involved in cancer. MiR2Pathway focuses on quantifying the differential effects of miRNAs on the activity of a biological pathway when miRNA-mRNA connections are altered from normal to disease and rank disease risk of rewired miRNA-mediated biological pathways. This dissertation explores how rewired gene-gene interactions and rewired miRNA-mRNA interactions lead to aberrant activity of biological pathways, and rank pathways for their disease risk. The two methods proposed here can be used to complement existing genomics analysis methods to facilitate the study of biological mechanisms behind disease at the systems-level.
ContributorsLi, Chaoxing (Author) / Dinu, Valentin (Thesis advisor) / Kuang, Yang (Thesis advisor) / Liu, Li (Committee member) / Wang, Xiao (Committee member) / Arizona State University (Publisher)
Created2017
Description
Childhood Apraxia of Speech (CAS) is a severe motor speech disorder that is difficult to diagnose as there is currently no gold-standard measurement to differentiate between CAS and other speech disorders. In the present study, we investigate underlying biomarkers associated with CAS in addition to enhanced phenotyping through behavioral testing. Cortical electrophysiological measures were utilized to investigate differences in neural activation in response to native and non-native vowel contrasts between children with CAS and typically developing peers. Genetic analysis included full exome sequencing of a child with CAS and his unaffected parents in order to uncover underlying genetic variation that may be causal to the child’s severely impaired speech and language. Enhanced phenotyping was completed through extensive behavioral testing, including speech, language, reading, spelling, phonological awareness, gross/fine motor, and oral and hand motor tasks. Results from cortical electrophysiological measures are consistent with previous evidence of a heightened neural response to non-native sounds in CAS, potentially indicating over specified phonological representations in this population. Results of exome sequencing suggest multiple genetic variations contributing to the severely affected phenotype in the child and provide further evidence of heterogeneous genomic pathways associated with CAS. Finally, results of behavioral testing demonstrate significant impairments evident across tasks in CAS, suggesting underlying sequential processing deficits in multiple domains. Overall, these results have the potential to delineate functional pathways from genetic variations to the brain to observable behavioral phenotypes and motivate the development of preventative and targeted treatment approaches.
ContributorsVose, Caitlin (Author) / Peter, Beate (Thesis advisor) / Liu, Li (Committee member) / Brewer, Gene (Committee member) / Arizona State University (Publisher)
Created2018
Description
Circular RNAs (circRNAs) are a class of endogenous, non-coding RNAs that are formed when exons back-splice to each other and represent a new area of transcriptomics research. Numerous RNA sequencing (RNAseq) studies since 2012 have revealed that circRNAs are pervasively expressed in eukaryotes, especially in the mammalian brain. While their functional role and impact remains to be clarified, circRNAs have been found to regulate micro-RNAs (miRNAs) as well as parental gene transcription and may thus have key roles in transcriptional regulation. Although circRNAs have continued to gain attention, our understanding of their expression in a cell-, tissue- , and brain region-specific context remains limited. Further, computational algorithms produce varied results in terms of what circRNAs are detected. This thesis aims to advance current knowledge of circRNA expression in a region specific context focusing on the human brain, as well as address computational challenges.
The overarching goal of my research unfolds over three aims: (i) evaluating circRNAs and their predicted impact on transcriptional regulatory networks in cell-specific RNAseq data; (ii) developing a novel solution for de novo detection of full length circRNAs as well as in silico validation of selected circRNA junctions using assembly; and (iii) application of these assembly based detection and validation workflows, and integrating existing tools, to systematically identify and characterize circRNAs in functionally distinct human brain regions. To this end, I have developed novel bioinformatics workflows that are applicable to non-polyA selected RNAseq datasets and can be used to characterize circRNA expression across various sample types and diseases. Further, I establish a reference dataset of circRNA expression profiles and regulatory networks in a brain region-specific manner. This resource along with existing databases such as circBase will be invaluable in advancing circRNA research as well as improving our understanding of their role in transcriptional regulation and various neurological conditions.
The overarching goal of my research unfolds over three aims: (i) evaluating circRNAs and their predicted impact on transcriptional regulatory networks in cell-specific RNAseq data; (ii) developing a novel solution for de novo detection of full length circRNAs as well as in silico validation of selected circRNA junctions using assembly; and (iii) application of these assembly based detection and validation workflows, and integrating existing tools, to systematically identify and characterize circRNAs in functionally distinct human brain regions. To this end, I have developed novel bioinformatics workflows that are applicable to non-polyA selected RNAseq datasets and can be used to characterize circRNA expression across various sample types and diseases. Further, I establish a reference dataset of circRNA expression profiles and regulatory networks in a brain region-specific manner. This resource along with existing databases such as circBase will be invaluable in advancing circRNA research as well as improving our understanding of their role in transcriptional regulation and various neurological conditions.
ContributorsSekar, Shobana (Author) / Liang, Winnie S (Thesis advisor) / Dinu, Valentin (Thesis advisor) / Craig, David (Committee member) / Liu, Li (Committee member) / Arizona State University (Publisher)
Created2018
Description
High childhood obesity rates have resulted in many interventions to attempt to lower these rates. Interventions such as day camps, residential camps, therapy-based interventions and family-based interventions lead to changes in weight and self-esteem but family-based intervention leads to the longest-term success for children ages nine to 17. Analysis of the interventions was measured using tools such as BMI, BMI-percentiles, and weight. Psychological measures such as self-esteem, happiness, and quality of life analysis was preferred, however were not measured in all studies. While most interventions resulted in weight loss and increased self-esteem, results were often not long-term. Studies provided evidence that family-based therapy has potential to last long-term, however there is a lack of research. To determine the most effective childhood nutrition intervention research must conduct follow-ups for many years after the initial intervention to ensure they provide long-term results.
ContributorsAnderson, Megan Lee (Author) / McCoy, Maureen (Thesis director) / Kniskern, Megan (Committee member) / College of Health Solutions (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
The purpose of this study was to develop proposal lesson plans for 4th-6th graders based on active learning to integrate movement physical activity into the curriculum. The 4th-6th graders were chosen, as this is the age where teaching typically transitions from active learning to sedentary/lecture style teaching. Research compiled indicated positive effects of active based learning on children such as increased attention span, retention, and general focus. A survey was created to not only assess the perception of active versus didactic learners, but to also assess the effects of movement-based learning on the variables that research claimed to change. The lesson plans developed here should be transferable to a classroom lesson to evaluate the hypothesized results.
ContributorsTanna, Nimisha (Author) / Hyatt, JP (Thesis director) / Ainsworth, Barbara (Committee member) / College of Health Solutions (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
About 75% of men and 66.58% of women are considered overweight or obese (BMI ≥25). $117 billion dollars is spent each year in medical costs due to physical inactivity. Aerobic exercise has been well defined in its’ benefits to cardiovascular health; however, the effects of resistance training are still not well defined. The purpose of this preliminary analysis was to evaluate the vascular health effects (central and peripheral blood pressure and VO2 max) of two different types of resistance training programs: high load, low repetitions resistance training and low load, high repetitions resistance training. Fourteen participants aged 18-55 years (6 males, 8 females) were involved in this preliminary analysis. Data were collected before and after the 12-week long exercise program (36 training sessions) via pulse wave analysis and VO2peak testing. Multivariate regression analysis of training program effects, while adjusting for body mass index and time, did not result in significant training effects on central and peripheral diastolic blood pressure, nor VO2peak. A statistical trend was observed between the different training programs for systolic blood pressure, suggesting that subjects partaking in the high load, low repetitions program exhibited higher systolic blood pressures than the low load, high repetitions group. With a larger sample size, the difference in systolic blood pressure may increase between training program groups and indicate that greater loads with minimal repetitions may increase lead to clinically significant elevations in blood pressure. Further work is needed to uncover the relationship between different types of resistance training and blood pressure, especially if these lifting regimens are continued for longer lengths of time.
ContributorsHill, Cody Alan (Co-author) / Hill, Cody (Co-author) / Whisner, Corrie (Thesis director) / Angadi, Siddhartha (Committee member) / College of Health Solutions (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Introduction: Individuals with rotator cuff tears have been found to compensate in their movement patterns by using lower thoracohumeral elevation angles during certain tasks, as well as increased internal rotation of the shoulder (Vidt et al., 2016). Leading joint hypothesis suggests there is one leading joint that creates the foundation for the entire limb motion, and there are other subordinate joints which monitor the passive interaction torque and create a net torque aiding to limb motions required for the task. This experiment seeks to establish a better understanding of joint control strategies during a wide range of arm movements. Based on the leading joint hypothesis, we hypothesize that when a subject has a rotator cuff tear, their performance of planar and three-dimensional motions should be altered not only at the shoulder, which is often the leading joint, but also at other joints on the arm, such as the elbow and wrist. This paper will focus on the effect of normal aging on the control of the joints of the arm.
Methods: There were 4 groups of participants: healthy younger adults (n=14)(21.74 ± 1.97), healthy older adults (n=12)(55-75), older adults (n=4)(55-75) with a partial-thickness rotator cuff tear, and older adults (n=4)(55-75) with a full-thickness rotator cuff tear (RCT). All four groups completed strength testing, horizontal drawing and pointing tasks, and three dimensional (3D) activities of daily living. Kinematic and kinetic variables of the arm were obtained during horizontal and 3D tasks using data from 12 reflective markers placed on the arm, 8 motion capture cameras, and Cortex motion capture software (Motion Analysis Corp., Santa Rosa, CA). Strength testing tasks were measured using a dynamometer. All strength testing and 3D tasks were completed for three trials and horizontal tasks were completed for two trials.
Results: Results of the younger adult participants showed that during the forward portion of seven 3D tasks, there were four phases of different joint control mechanics seen in a majority of the movements. These phases included active rotation of both the shoulder and the elbow joint, active rotation of the shoulder with passive rotation of the elbow, passive rotation of the shoulder with active rotation of the elbow, and passive rotation of both the shoulder and the elbow. Passive rotation during movements was a result of gravitational torque on the different segments of the arm and interaction torque caused as a result of the multi-joint structure of human limbs. The number of tested participants for the minor RCT, and RCT older adults groups is not yet high enough to produce significant results and because of this their results are not reported in this article. Between the older adult control group and the young adult control group in the tasks upward reach to eye height and hair comb there were significant differences found between the groups. The differences were found in shorter overall time and distance between the two groups in the upward eye task.
Discussion: Through the available results, multiple phases were found where one or both of the joints of the arm moved passively which further supports the LJH and extends it to include 3D movements. With available data, it can be concluded that healthy older adults use movement control strategies, such as shortening distance covered, decreasing time percentage in active joint phases, and increasing time percentage in passive joint phases, to account for atrophy along with other age-related declines in performance, such as a decrease in range of motion. This article is a part of a bigger project which aims to better understand how older adults with RCTs compensate for the decreased strength, the decreased range of motion, and the pain that accompany this type of injury. It is anticipated that the results of this experiment will lead to more research toward better understanding how to treat patients with RCTs.
Methods: There were 4 groups of participants: healthy younger adults (n=14)(21.74 ± 1.97), healthy older adults (n=12)(55-75), older adults (n=4)(55-75) with a partial-thickness rotator cuff tear, and older adults (n=4)(55-75) with a full-thickness rotator cuff tear (RCT). All four groups completed strength testing, horizontal drawing and pointing tasks, and three dimensional (3D) activities of daily living. Kinematic and kinetic variables of the arm were obtained during horizontal and 3D tasks using data from 12 reflective markers placed on the arm, 8 motion capture cameras, and Cortex motion capture software (Motion Analysis Corp., Santa Rosa, CA). Strength testing tasks were measured using a dynamometer. All strength testing and 3D tasks were completed for three trials and horizontal tasks were completed for two trials.
Results: Results of the younger adult participants showed that during the forward portion of seven 3D tasks, there were four phases of different joint control mechanics seen in a majority of the movements. These phases included active rotation of both the shoulder and the elbow joint, active rotation of the shoulder with passive rotation of the elbow, passive rotation of the shoulder with active rotation of the elbow, and passive rotation of both the shoulder and the elbow. Passive rotation during movements was a result of gravitational torque on the different segments of the arm and interaction torque caused as a result of the multi-joint structure of human limbs. The number of tested participants for the minor RCT, and RCT older adults groups is not yet high enough to produce significant results and because of this their results are not reported in this article. Between the older adult control group and the young adult control group in the tasks upward reach to eye height and hair comb there were significant differences found between the groups. The differences were found in shorter overall time and distance between the two groups in the upward eye task.
Discussion: Through the available results, multiple phases were found where one or both of the joints of the arm moved passively which further supports the LJH and extends it to include 3D movements. With available data, it can be concluded that healthy older adults use movement control strategies, such as shortening distance covered, decreasing time percentage in active joint phases, and increasing time percentage in passive joint phases, to account for atrophy along with other age-related declines in performance, such as a decrease in range of motion. This article is a part of a bigger project which aims to better understand how older adults with RCTs compensate for the decreased strength, the decreased range of motion, and the pain that accompany this type of injury. It is anticipated that the results of this experiment will lead to more research toward better understanding how to treat patients with RCTs.
ContributorsFlores, Noah Mateo (Author) / Dounskaia, Natalia (Thesis director) / Vidt, Meghan (Committee member) / College of Health Solutions (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
After volunteering at a clinic in Guatemala and seeing the sexism that is so engrained into their culture, I decided to take a look at the U.S. healthcare system. I wanted to uncover the stereotypes, statistics and gender and societal norms that are present in our culture. I first started with the application process and the acceptance rates to medical school. I discovered that men are accepted to medical school at higher rates than women unless that man is deemed dangerous or foreign. I then moved on to the environment in medical school. Many women are subjected to snide comments or “bro talk” made to make them feel inferior. Men always graduate at higher rates than women, which could be because of the unwelcoming environment in medical school or the lack of female faculty chairs or mentors. After medical school, a new doctor must choose a specialty. Men gravitate towards specialties that focus on surgical work and large sums of money. Women tend to choose specialties that require a more soothing and caring environment. Women are more likely to pick specialties where there is a higher proportion of female residents. After specialties, I then explored the life of a doctor. Slightly over half of all doctors in the workforce are men and they make an average of $78,288 more per year than female physicians. Women are discriminated against if they become pregnant on the job and they are more likely to develop mental health issues. Female physicians are overall, more compassionate, rule abiding and patient-focused than their male counterparts but are not receiving the acknowledgments that they deserve. After delving into the U.S. healthcare system, I have realized that sexism in the workforce is blatantly apparent and is one of the outcomes of our patriarchal society. The only way we can make a change is to acknowledge the problem and come together as a society to combat the issue.
ContributorsPurkey, Caroline Rose (Author) / Collins, Michael (Thesis director) / Barry, Anne (Committee member) / College of Health Solutions (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
There has been a rise in the prevalence of mental health disorders among western industrialized populations.1 By 2020, depression will be second to heart disease in its contribution to the global burden of disease as measured by disability-adjusted life years.2 Anxiety disorders are the most common mental illness in the U.S., affecting 40 million adults in the United States ages 18 and older, or 18.1% of the U.S population every year.3
Mental disorders are prevalent in young adults and frequently present between 12-24 years of age.4 The top five sources of stress reported by college students were changes in sleeping routines, changes in eating habits, increased amount of work, new responsibilities, and breaks/vacations.5 Overall, a total of 73% of college students report occasional difficulties sleeping, and 48% of students suffer from sleep deprivation, as self-reported.6,7
Lifestyle factors such as diet, exercise and sleep may influence symptoms related to stress and depression.8 Symptoms of depression include but are not limited to, persistent anxious or sad moods, feeling guilty or helpless, loss of interest in hobbies, irritability, and other behaviors that may interrupt daily living.9 Inadequate intake of folic acid from fruits and vegetables, and essential fatty acids in fish, may increase symptoms of depression.10 Unhealthy eating habits may be associated with increases in depression-like symptoms in women, supporting the notion that healthier eating habits may decrease major depression.11 Diet is only one component of how lifestyle may influence depression and stress in adults. Exercise may be another important component in decreasing depression-related symptoms due to the release of endorphins.12 It has been found that participating in regular physical activity may decrease tension levels, increase and stabilize mood, improve self-esteem, and lead to better sleeping patterns.13 It has been concluded that individuals who consume a healthy diet are less likely to experience depression whereas people eating unhealthy and processed diets are more likely to be depressed.14
Poor sleep quality as well as unstable sleeping patterns may lead to poor psychological and physical health.15 Poor sleep includes longer duration of sleep onset latency, which is defined as the amount of time it takes to fall asleep, waking up multiple times throughout the night, and not getting a restful sleep because of tossing and turning.16 In healthy adults, the short-term consequences of sleep disruption consist of somatic pain, emotional destress and mood disorders, reduced quality of life, and increased stress responsivity.17 Irregular sleep-wake patterns, defined as taking numerous naps within a 24 hour span and not having a main nighttime sleep experience, are present at alarming levels (more than a quarter) among college students.18 A study done with 2,000 college students concluded that more than a quarter of the students were at risk of a sleeping disorder.19 Therefore, college students who were classified as poor-quality sleepers, reported experiencing more psychological and physical health problems compared to their healthy counterparts. Perceived stress was also found to be a factor in lower sleep quality of young adults.20
The link between depression-like symptoms and sleep remains poorly understood. It is mentioned that there are risk factors of poor sleep, depression and anxiety among college students but this topic has not yet been heavily studied within this population.
Mental disorders are prevalent in young adults and frequently present between 12-24 years of age.4 The top five sources of stress reported by college students were changes in sleeping routines, changes in eating habits, increased amount of work, new responsibilities, and breaks/vacations.5 Overall, a total of 73% of college students report occasional difficulties sleeping, and 48% of students suffer from sleep deprivation, as self-reported.6,7
Lifestyle factors such as diet, exercise and sleep may influence symptoms related to stress and depression.8 Symptoms of depression include but are not limited to, persistent anxious or sad moods, feeling guilty or helpless, loss of interest in hobbies, irritability, and other behaviors that may interrupt daily living.9 Inadequate intake of folic acid from fruits and vegetables, and essential fatty acids in fish, may increase symptoms of depression.10 Unhealthy eating habits may be associated with increases in depression-like symptoms in women, supporting the notion that healthier eating habits may decrease major depression.11 Diet is only one component of how lifestyle may influence depression and stress in adults. Exercise may be another important component in decreasing depression-related symptoms due to the release of endorphins.12 It has been found that participating in regular physical activity may decrease tension levels, increase and stabilize mood, improve self-esteem, and lead to better sleeping patterns.13 It has been concluded that individuals who consume a healthy diet are less likely to experience depression whereas people eating unhealthy and processed diets are more likely to be depressed.14
Poor sleep quality as well as unstable sleeping patterns may lead to poor psychological and physical health.15 Poor sleep includes longer duration of sleep onset latency, which is defined as the amount of time it takes to fall asleep, waking up multiple times throughout the night, and not getting a restful sleep because of tossing and turning.16 In healthy adults, the short-term consequences of sleep disruption consist of somatic pain, emotional destress and mood disorders, reduced quality of life, and increased stress responsivity.17 Irregular sleep-wake patterns, defined as taking numerous naps within a 24 hour span and not having a main nighttime sleep experience, are present at alarming levels (more than a quarter) among college students.18 A study done with 2,000 college students concluded that more than a quarter of the students were at risk of a sleeping disorder.19 Therefore, college students who were classified as poor-quality sleepers, reported experiencing more psychological and physical health problems compared to their healthy counterparts. Perceived stress was also found to be a factor in lower sleep quality of young adults.20
The link between depression-like symptoms and sleep remains poorly understood. It is mentioned that there are risk factors of poor sleep, depression and anxiety among college students but this topic has not yet been heavily studied within this population.
ContributorsBosnino, Jasmine (Co-author, Co-author) / Whisner, Corrie (Thesis director) / Petrov, Megan (Committee member) / Mahmood, Tara (Committee member) / College of Health Solutions (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Patients face tremendous challenges when attempting to navigate the United States health care system. This difficulty to navigate the system creates a burden that is placed on the patient and caregiver, in turn affecting the health outcomes of the patient, resulting in higher health care costs, less than desirable outcomes, and a large strain on the patient and caregiver's daily lives. There are several ways that people have tried to create a comprehensive theoretical framework to understand the system from multiple perspectives. This work will expand existing theoretical frameworks that observes the relationship between the patient, their social networks, and health care services such as the Burden of Treatment Theory. Consisting of a comprehensive, multidisciplinary literature review, research was derived from the disciplines of medicine, informatics, management, and ethics. In this paper, I attempt to identify key contributing factors and then develop and categorize these stressors into a typology. Since there are many contributing factors that affect the burden of work at multiple levels, a nested typology will be used which will link micro- and macro-leveled pressures to a single system while also showcasing how each level interacts and is influenced by the others. For the categorization of the contributing factors, they will be sorted into individual actors, organizational level, and macro-level factors. The implications of this work suggest that a combination of historical shifts, structural design, and secondary effects of policy contribute to patients' burden of work.
ContributorsTomlinson, Rachel Laiku (Author) / Pine, Katie (Thesis director) / Trinh, Mai (Committee member) / School for the Science of Health Care Delivery (Contributor) / Barrett, The Honors College (Contributor) / College of Health Solutions (Contributor)
Created2017-05