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- Genre: Masters Thesis
Description
Pathogenic Gram-negative bacteria employ a variety of molecular mechanisms to combat host defenses. Two-component regulatory systems (TCR systems) are the most ubiquitous signal transduction systems which regulate many genes required for virulence and survival of bacteria. In this study, I analyzed different TCR systems in two clinically-relevant Gram-negative bacteria, i.e., oral pathogen Porphyromonas gingivalis and enterobacterial Escherichia coli. P. gingivalis is a major causative agent of periodontal disease as well as systemic illnesses, like cardiovascular disease. A microarray study found that the putative PorY-PorX TCR system controls the secretion and maturation of virulence factors, as well as loci involved in the PorSS secretion system, which secretes proteinases, i.e., gingipains, responsible for periodontal disease. Proteomic analysis (SILAC) was used to improve the microarray data, reverse-transcription PCR to verify the proteomic data, and primer extension assay to determine the promoter regions of specific PorX regulated loci. I was able to characterize multiple genetic loci regulated by this TCR system, many of which play an essential role in hemagglutination and host-cell adhesion, and likely contribute to virulence in this bacterium. Enteric Gram-negative bacteria must withstand many host defenses such as digestive enzymes, low pH, and antimicrobial peptides (AMPs). The CpxR-CpxA TCR system of E. coli has been extensively characterized and shown to be required for protection against AMPs. Most recently, this TCR system has been shown to up-regulate the rfe-rff operon which encodes genes involved in the production of enterobacterial common antigen (ECA), and confers protection against a variety of AMPs. In this study, I utilized primer extension and DNase I footprinting to determine how CpxR regulates the ECA operon. My findings suggest that CpxR modulates transcription by directly binding to the rfe promoter. Multiple genetic and biochemical approaches were used to demonstrate that specific TCR systems contribute to regulation of virulence factors and resistance to host defenses in P. gingivalis and E. coli, respectively. Understanding these genetic circuits provides insight into strategies for pathogenesis and resistance to host defenses in Gram negative bacterial pathogens. Finally, these data provide compelling potential molecular targets for therapeutics to treat P. gingivalis and E. coli infections.
ContributorsLeonetti, Cori (Author) / Shi, Yixin (Thesis advisor) / Stout, Valerie (Committee member) / Nickerson, Cheryl (Committee member) / Sandrin, Todd (Committee member) / Arizona State University (Publisher)
Created2013
Description
The relationship between ischemic preconditioning and performance measures in able-bodied athletic populations have been thoroughly studied within the literature and demonstrated significant performance improvements. However, there is currently only one human study investigating how IPC can impact performance measures in individuals with a spinal cord injury (SCI). The mechanism that influences these performance improvements is still not fully understood. The purpose of this study was to investigate the effects of IPC in this population on performance measures, muscular force, and neural contribution. This study utilized 4 participants who have experienced a SCI. The study design was a repeated-measures, cross-over model. It consisted of an IPC (220mmHg) and SHAM (20mmHg) condition in random order. Functional measures of skeletal muscle force and neural measures with surface electromyography were recorded. The performance measures were maximum voluntary contractions (MVC) of the forearm muscles and a time to task failure (TTF) handgrip test. Results: IPC did not improve performance output between both conditions in a TTF handgrip test (IPC: 25.295±10.371 mins; SHAM: 20.958±7.621 mins). IPC did not improve muscular force recorded as MVC (IPC: 571.38 241.83 N; SHAM: 543.32±210.89 N). IPC did not improve neural recruitment suggested in root mean square (RMS) values during the TTF handgrip test in both measured muscles, the flexor carpi radialis (FCR) and the flexor carpi ulnaris (FCU), (FCR RMS: p = 0.564; FCU RMS: p = 0.863). More data is need for statistical relevance and to determine if there is a relationship between IPC and performance in individuals who have experienced a SCI, and if neural contribution plays a role.
ContributorsKasofsky, Lexi (Author) / Siegler, Jason (Thesis advisor) / Williams, Candyce (Committee member) / Peterson, Daniel (Committee member) / Holzapfel, Simon (Committee member) / Arizona State University (Publisher)
Created2022
Description
Shoulder injuries are common in major league baseball (MLB) players due to the explosive and unnatural throwing motion. The goal of the thesis was to provide quantitative information about factors that influence pitching outcomes, to better understand risk management of rotator cuff tears/injuries. Typically, shoulder injuries are due to the stress placed on the glenohumeral joint. While the kinetic chain and joint muscular forces produce the explosive overhead throw. There’s a vast range when it comes to shoulder injuries for pitchers. Rotator cuff injuries are common, and multiple factors contribute to either impingement/strains, tendinitis, or tears. The purpose of this study was to assess shoulder injuries sustained by MLB pitchers between 2015-2021, to identify changes between performance metrics, collected from a publicly available database for differences between pre and post injury. Selected factors of interest are: playing years in the league, injury history, average pitch types thrown for both preinjury and postinjury, release speed, release position in the x, y, and z directions, horizontal and vertical movement, horizontal and vertical positions of the ball when it crosses home plate (plate_x and plate_z), resultant velocities and accelerations, release spin rate, release extension, spin axis and return-to-sport determined by length of time spent on the injured list (IL) for more than 100 days or less than 100 days. Resultant velocities and accelerations were calculated using the provided metrics for velocity and acceleration in the x, y, z global dimensions. Resultant velocities were significant only for off-speed pitches (P= 0.053). Multiple linear regression analysis was preformed to relate ball flight kinematics (displacement, ball velocity, and acceleration), angular kinematics (spin rate and spin axis) per each pitch bin (e.g., fastballs, breaking balls, and off-speed pitches) to relate performance metrics found prior to injury and those after the sustained injury. Ball speed in miles per hour presented significance in the off-speed pitches, though spin rate was only significant for breaking ball pitches. Two distinct spin axis orientations were significant: breaking balls and off-speed pitches. The horizontal release position was significant for both fastballs and breaking balls than in the vertical release position which was significant for all pitch bins. From the analysis of variance, inferences were made to additional factors of interest that are out of the scope such as, kinematic sequence velocities and ground reaction forces.
ContributorsWalsh, McKenzie (Author) / Ofori, Edward (Thesis advisor) / Siegler, Jason (Committee member) / Peterson, Daniel (Committee member) / Arizona State University (Publisher)
Created2022
Description
The present study aimed to compare brain activity changes related to proactive and reactive control strategies in patients with Parkinson’s disease during “On” levodopa and “Off” levodopa conditions. The study consisted of two participants who had received a prior diagnosis of Parkinson’s Disease. The participants completed AX-CPT task as a measure of attention control in two sessions: a) “On Levodopa” and b) “Off Levodopa” while they were in the fMRI scanner. Prior to the analysis, the T1- weighted anatomical scan images and the BOLD multiband functional images of both the participants were BIDS (Brain Imaging Data Structure) validated and preprocessed using the standard FMRIPrep pipeline. The imaging data was then analyzed using SPM12 (Statistical parametric mapping) software. Individual-level analysis of the imaging data was conducted by creating General Linear models for both the participants on “ON” and “OFF” levodopa conditions. The BOLD responses were compared using AY>BY and BX > BY contrasts. Where BX >, BY contrast, measured BOLD activity related to reactive control strategy and AY> BY contrast measured BOLD activity related to the proactive control strategy. It was observed that participants tended towards reactive control strategy in both “On” and “Off” levodopa conditions.
ContributorsDatta, Kalyani (Author) / Brewer, Gene (Thesis advisor) / Braden, B. Blair (Committee member) / Peterson, Daniel (Committee member) / Arizona State University (Publisher)
Created2022
Description
Fine control of standing postural balance is essential for completing various tasks in daily activities, which might be compromised when interacting with dynamically challenging environments (e.g., moving ground). Among various biofeedback to improve postural balance control, vibrotactile feedback has an advantage of providing supplementary information about balance control without disturbing other core functions (e.g., seeing and hearing). This paper investigated the effectiveness of a waist vibrotactile feedback device to improve postural control during standing balance on a dynamically moving ground simulated by a robotic balance platform. Four vibration motors of the waist device applied vibration feedback in the anterior-posterior and medio-lateral direction based on the 2-dimensional sway angle, measured by an inertia measurement unit. Experimental results with 15 healthy participants demonstrated that the waist vibrotactile feedback is effective in improving postural control, evidenced by improvements in center-of-mass and center-of-pressure stability measures. In addition, this study confirmed the effectiveness of the waist vibrotactile feedback in improving standing balance control even under muscle fatigue induced by lower body exercise. The study further confirmed that the waist feedback is more effective in people with lower baseline balance performance in both normal and fatigue conditions.
ContributorsJo, Kwanghee (Author) / Lee, Hyunglae (Thesis advisor) / Sugar, Thomas (Committee member) / Peterson, Daniel (Committee member) / Arizona State University (Publisher)
Created2022
Description
Parkinson’s Disease is one of the most complicated and abundantneurodegenerative diseases in the world. Previous analysis of Parkinson’s disease has
identified both speech and gait deficits throughout progression of the disease. There has
been minimal research looking into the correlation between both the speech and gait
deficits in those diagnosed with Parkinson’s. There is high indication that there is a
correlation between the two given the similar pathology and origins of both deficits. This
exploratory study aims to establish correlation between both the gait and speech deficits
in those diagnosed with Parkinson’s disease. Using previously identified motor and
speech measurements and tasks, I conducted a correlational study of individuals with
Parkinson’s disease at baseline. There were correlations between multiple speech and gait
variability outcomes. The expected correlations ranged from average harmonics-to-noise
ratio values against anticipatory postural adjustments-lateral peak distance to average
shimmer values against anticipatory postural adjustments-lateral peak distance. There
were also unexpected outcomes that ranged from F2 variability against the average
number of steps in a turn to intensity variability against step duration variability. I also
analyzed the speech changes over 1 year as a secondary outcome of the study. Finally, I
found that averages and variabilities increased over 1 year regarding speech primary
outcomes. This study serves as a basis for further treatment that may be able to
simultaneously treat both speech and gait deficits in those diagnosed with Parkinson’s.
The exploratory study also indicates multiple targets for further investigation to better
understand cohesive and compensatory mechanisms.
ContributorsBelnavis, Alexander Salvador (Author) / Peterson, Daniel (Thesis advisor) / Daliri, Ayoub (Committee member) / Berisha, Visar (Committee member) / Arizona State University (Publisher)
Created2022
Description
This thesis work presents two separate studies:The first study assesses standing balance under various 2-dimensional (2D) compliant environments simulated using a dual-axis robotic platform and vision conditions. Directional virtual time-to-contact (VTC) measures were introduced to better characterize postural balance from both temporal and spatial aspects, and enable prediction of fall-relevant directions. Twenty healthy young adults were recruited to perform quiet standing tasks on the platform. Conventional stability measures, namely center-of-pressure (COP) path length and COP area, were also adopted for further comparisons with the proposed VTC. The results indicated that postural balance was adversely impacted, evidenced by significant decreases in VTC and increases in COP path length/area measures, as the ground compliance increased and/or in the absence of vision (ps < 0.001). Interaction effects between environment and vision were observed in VTC and COP path length measures (ps ≤ 0.05), but not COP area (p = 0.103). The estimated likelihood of falls in anterior-posterior (AP) and medio-lateral (ML) directions converged to nearly 50% (almost independent of the foot setting) as the experimental condition became significantly challenging.
The second study introduces a deep learning approach using convolutional neural network (CNN) for predicting environments based on instant observations of sway during balance tasks. COP data were collected from fourteen subjects while standing on the 2D compliant environments. Different window sizes for data segmentation were examined to identify its minimal length for reliable prediction. Commonly-used machine learning models were also tested to compare their effectiveness with that of the presented CNN model. The CNN achieved above 94.5% in the overall prediction accuracy even with 2.5-second length data, which cannot be achieved by traditional machine learning models (ps < 0.05). Increasing data length beyond 2.5 seconds slightly improved the accuracy of CNN but substantially increased training time (60% longer). Importantly, averaged normalized confusion matrices revealed that CNN is much more capable of differentiating the mid-level environmental condition.
These two studies provide new perspectives in human postural balance, which cannot be
interpreted by conventional stability analyses. Outcomes of these studies contribute to the advancement of human interactive robots/devices for fall prevention and rehabilitation.
ContributorsPhan, Vu Nguyen (Author) / Lee, Hyunglae (Thesis advisor) / Peterson, Daniel (Committee member) / Marvi, Hamidreza (Committee member) / Arizona State University (Publisher)
Created2021
Description
Cannabis use is increasing both medically and recreationally. Over the last decade studies have investigated sex differences associated with Parkinson’s disease (PD) diagnosis and degenerative symptoms. Previous research has shown that cannabis use has had either a beneficial or deleterious effect on PD symptoms. This research will examine whether sex differences exist among the positive or negative effects of cannabis use in PD. In this paper, an analysis of sex-based differences between male and female cohorts categorized across 2,700 participants is completed under the Fox Insight data set. Each cohort will be compared to 14 nonmotor symptoms and 8 motor symptoms commonly associated with PD. In each cohort mean age, cannabis intake, cannabis dose, cannabis type, and PD diagnosis are analyzed within groups. Each symptom (motor and nonmotor) was analyzed between cohort responses to indicate if there was beneficial or worsening effect within cannabis. Results indicated that the designated female cohort reported both beneficial and worsening effects of cannabis use regarding both motor and nonmotor symptoms. The positive symptoms primarily consisted of individual motor functioning (e.g. dyskinesia, stiffness, back pain, etc.) while the worsening symptoms primarily consisted of nonmotor functioning (e.g. anxiety and apathy). Meanwhile, the male cohort only reported beneficial effects towards nonmotor symptoms (e.g. dystonia, muscle cramps, heart rate). These findings suggest the need for further examination of nigrostriatal pathways and hypothalamic integrity in PD, as it may provide more information into the effects of cannabis use based on sex differences.
ContributorsHooten, Madeline Loraine (Author) / Ofori, Edward (Thesis advisor) / Daniulaityte, Raminta (Committee member) / Peterson, Daniel (Committee member) / Arizona State University (Publisher)
Created2022
Description
Chronic ankle instability (CAI) is caused by the failure to seek treatment and rehabilitation after an acute ankle sprain. Typically, clinical assessment of ankle sprains is done under unloaded conditions, despite the fact that ankle sprains occur during weight loading. Characterization of ankle stiffness, a representation of ankle stability during weight loading, is crucial to quantify ankle stability. Patients with CAI suffer from gait asymmetry, and the descriptions of the asymmetry ratio vary widely throughout the research community. Bilateral ankle stiffness could be a systematic metric to describe the gait asymmetry of CAI patients. Additionally, women generally have higher ankle joint and ligamentous laxity than men, and lower ankle stiffness, which has been thoroughly investigated in previous literature. However, differences in bilateral ankle stiffness between sexes still need to be investigated. Using twin dual-axis robotic platforms, this study investigated the weight loading effect on ankle stiffness in the frontal plane during standing, the bilateral difference in stiffness between the dominant and non-dominant ankle, and the sex difference in bilateral ankle stiffness during standing for varying weight distribution. The group average results of 20 healthy subjects showed that ankle stiffness increased with increasing weight loading on the ankle, which is speculated to be caused by active muscle contraction and changes in passive structure due to weight loading. For the bilateral difference of the group, the statistical analysis showed that there was no significant difference between dominant and non-dominant ankle stiffness for all the weight distributions considered. Although the group average result of the difference in bilateral ankle stiffness was statistically insignificant, individual analysis confirmed the importance of subject-specific investigation of bilateral ankle stiffness, as there were more cases of dominant ankle stiffness being larger than non-dominant ankle stiffness, and the bilateral difference was subject-specific. Investigations into sex differences in bilateral ankle stiffness showed that ankle stiffness in males is significantly greater than in females, even after normalizing the stiffness by weight, which is speculated to be caused by higher joint and ligamentous laxity in females regardless of laterality.
ContributorsPaing, Soe Lin (Author) / Lee, Hyunglae (Thesis advisor) / Berman, Spring (Committee member) / Peterson, Daniel (Committee member) / Arizona State University (Publisher)
Created2023
Description
Many Fic domain proteins, through catalyzing post translational modifications (PTM) of protein substrates, functionally contribute to bacterial pathogenesis and the regulation of bacterial growth. Furthermore, one form of Fic-mediated regulation is the Fic toxin-antitoxin system, whereby an antitoxin interacts with and inhibits the Fic toxin. This study sought to determine the functional importance of Mycobacterium tuberculosis Fic and its putative antitoxin protein, Rv3642c. Using M. tuberculosis H37Rv genetic deletion mutants, fic and Rv3642c were demonstrated to promote intracellular survival in human THP-1 macrophage-like cells. Unlike other Fic toxins, of Fic toxin-antitoxin systems, Fic did not inhibit bacterial growth in vitro in the absence of Rv3642c. Notably, Fic demonstrated in vitro AMPylation of a THP-1 cell extract protein as shown by immunodetection. Fic also exhibited auto-AMPylation activity. Interestingly, a mutation of the conserved histidine in the Fic domain motif, a residue previously shown to be critical for AMPylation, had no effect on Fic-mediated ATP hydrolysis or AMPylation activity. Rv3642c was demonstrated to form a complex with Fic when co-expressed in Escherichia coli, indicating a toxin-antitoxin interaction. Screening M. tuberculosis protein fractions and culture filtrate with α-Fic and α-Rv3642c rabbit antisera did not detect monomers of Fic or Rv3642c, thus the cellular localization of Fic and the Rv3642c-Fic complex remains unclear. The results of this study provide insight into the function of M. tuberculosis Fic, and suggest that Fic and Rv3642c are important for M. tuberculosis survival in the intracellular macrophage environment. Furthermore, these findings challenge the current dogma that Fic domain catalysis is dependent on the conserved histidine of the Fic motif.
ContributorsLaMarca, Ryan (Author) / Haydel, Shelley (Thesis advisor) / Lake, Douglas (Committee member) / Nickerson, Cheryl (Committee member) / Arizona State University (Publisher)
Created2017