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This research project investigated known and novel differential genetic variants and their associated molecular pathways involved in Type II diabetes mellitus for the purpose of improving diagnosis and treatment methods. The goal of this investigation was to 1) identify the genetic variants and SNPs in Type II diabetes to develop a gene regulatory pathway, and 2) utilize this pathway to determine suitable drug therapeutics for prevention and treatment. Using a Gene Set Enrichment Analysis (GSEA), a set of 1000 gene identifiers from a Mayo Clinic database was analyzed to determine the most significant genetic variants related to insulin signaling pathways involved in Type II Diabetes. The following genes were identified: NRAS, KRAS, PIK3CA, PDE3B, TSC1, AKT3, SOS1, NEU1, PRKAA2, AMPK, and ACC. In an extensive literature review and cross-analysis with Kegg and Reactome pathway databases, novel SNPs located on these gene variants were identified and used to determine suitable drug therapeutics for treatment. Overall, understanding how genetic mutations affect target gene function related to Type II Diabetes disease pathology is crucial to the development of effective diagnosis and treatment. This project provides new insight into the molecular basis of the Type II Diabetes, serving to help untangle the regulatory complexity of the disease and aid in the advancement of diagnosis and treatment. Keywords: Type II Diabetes mellitus, Gene Set Enrichment Analysis, genetic variants, KEGG Insulin Pathway, gene-regulatory pathway
ContributorsBucklin, Lindsay (Co-author) / Davis, Vanessa (Co-author) / Holechek, Susan (Thesis director) / Wang, Junwen (Committee member) / Nyarige, Verah (Committee member) / School of Human Evolution & Social Change (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
This research project investigated known and novel differential genetic variants and their associated molecular pathways involved in Type II diabetes mellitus for the purpose of improving diagnosis and treatment methods. The goal of this investigation was to 1) identify the genetic variants and SNPs in Type II diabetes to develop a gene regulatory pathway, and 2) utilize this pathway to determine suitable drug therapeutics for prevention and treatment. Using a Gene Set Enrichment Analysis (GSEA), a set of 1000 gene identifiers from a Mayo Clinic database was analyzed to determine the most significant genetic variants related to insulin signaling pathways involved in Type II Diabetes. The following genes were identified: NRAS, KRAS, PIK3CA, PDE3B, TSC1, AKT3, SOS1, NEU1, PRKAA2, AMPK, and ACC. In an extensive literature review and cross-analysis with Kegg and Reactome pathway databases, novel SNPs located on these gene variants were identified and used to determine suitable drug therapeutics for treatment. Overall, understanding how genetic mutations affect target gene function related to Type II Diabetes disease pathology is crucial to the development of effective diagnosis and treatment. This project provides new insight into the molecular basis of the Type II Diabetes, serving to help untangle the regulatory complexity of the disease and aid in the advancement of diagnosis and treatment.
ContributorsDavis, Vanessa Brooke (Co-author) / Bucklin, Lindsay (Co-author) / Holechek, Susan (Thesis director) / Wang, Junwen (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Most daily living tasks consist of pairing a series of sequential movements, e.g., reaching to a cup, grabbing the cup, lifting and returning the cup to your mouth. The process by which we control and mediate the smooth progression of these tasks is not well understood. One method which we can use to further evaluate these motions is known as Startle Evoked Movements (SEM). SEM is an established technique to probe the motor learning and planning processes by detecting muscle activation of the sternocleidomastoid muscles of the neck prior to 120ms after a startling stimulus is presented. If activation of these muscles was detected following a stimulus in the 120ms window, the movement is classified as Startle+ whereas if no sternocleidomastoid activation is detected after a stimulus in the allotted time the movement is considered Startle-. For a movement to be considered SEM, the activation of movements for Startle+ trials must be faster than the activation of Startle- trials. The objective of this study was to evaluate the effect that expertise has on sequential movements as well as determining if startle can distinguish when the consolidation of actions, known as chunking, has occurred. We hypothesized that SEM could distinguish words that were solidified or chunked. Specifically, SEM would be present when expert typists were asked to type a common word but not during uncommon letter combinations. The results from this study indicated that the only word that was susceptible to SEM, where Startle+ trials were initiated faster than Startle-, was an uncommon task "HET" while the common words "AND" and "THE" were not. Additionally, the evaluation of the differences between each keystroke for common and uncommon words showed that Startle was unable to distinguish differences in motor chunking between Startle+ and Startle- trials. Explanations into why these results were observed could be related to hand dominance in expert typists. No proper research has been conducted to evaluate the susceptibility of the non-dominant hand's fingers to SEM, and the results of future studies into this as well as the results from this study can impact our understanding of sequential movements.
ContributorsMieth, Justin Richard (Author) / Honeycutt, Claire (Thesis director) / Santello, Marco (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Startle-evoked-movement (SEM), the involuntary release of a planned movement via a startling stimulus, has gained significant attention recently for its ability to probe motor planning as well as enhance movement of the upper extremity following stroke. We recently showed that hand movements are susceptible to SEM. Interestingly, only coordinated movements of the hand (grasp) but not individuated movements of the finger (finger abduction) were susceptible. It was suggested that this resulted from different neural mechanisms involved in each task; however it is possible this was the result of task familiarity. The objective of this study was to evaluate a more familiar individuated finger movement, typing, to determine if this task was susceptible to SEM. We hypothesized that typing movements will be susceptible to SEM in all fingers. These results indicate that individuated movements of the fingers are susceptible to SEM when the task involves a more familiar task, since the electromyogram (EMG) latency is faster in SCM+ trials compared to SCM- trials. However, the middle finger does not show a difference in terms of the keystroke voltage signal, suggesting the middle finger is less susceptible to SEM. Given that SEM is thought to be mediated by the brainstem, specifically the reticulospinal tract, this suggest that the brainstem may play a role in movements of the distal limb when those movements are very familiar, and the independence of each finger might also have a significant on the effect of SEM. Further research includes understanding SEM in fingers in the stroke population. The implications of this research can impact the way upper extremity rehabilitation is delivered.
ContributorsQuezada Valladares, Maria Jose (Author) / Honeycutt, Claire (Thesis director) / Santello, Marco (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Research on human grasp typically involves the grasp of objects designed for the study of fingertip forces. Instrumented objects for such studies have often been designed for the simulation of functional tasks, such as feeding oneself, or for rigidity such that the objects do not deform when grasped. The goal of this thesis was to design a collapsible, instrumented object to study grasp of breakable objects. Such an object would enable experiments on human grip responses to unexpected finger-object events as well as anticipatory mechanisms once object fragility has been observed. The collapsible object was designed to be modular to allow for properties such as friction and breaking force to be altered. The instrumented object could be used to study both human and artificial grasp.
ContributorsTorrez, Troy (Author) / Santos, Veronica (Thesis director) / Santello, Marco (Committee member) / Artemiadis, Panagiotis (Committee member) / Barrett, The Honors College (Contributor)
Created2012-05
Description
Telestroke networks reduce disparities in acute stroke care between metropolitan primary stroke centers and remote hospitals. Current technologies used to conduct remote patient assessments have very high start-up costs, yet they cannot consistently establish quality connection in a timely manner. Smartphgones can be used for high quality video teleconferencing (HQ-VTC). They are relatively inexpensive and widley used among healthcare providers. We aimed to study the reliability of HQ-VTC using smartphones for conducting the NIHSS. Two vascular neurologists (VNs) assessed 83 stroke patients with the NIHSS. The remote VN assessed patients using videoconferencing on a smartphone with the assistance of a bedside medical aide. The bedside VN rated patients ontemporaneously. Each VN was blinded to the other's NIHSS scores. We tested the inter-method agreement and physician satisfaction with the device. We demonstrated high total NIHSS score correlation between the methods (r=0.941, p<0.001). The mean total NIHSS scores for bedside and remote assessments were 7.3 plus or minus 7.9 and 6.7 plus or minus 7.6 with ranges of 0-30 and 0-37, respectively. Seven NIHSS categories had significantly high agreement beyond chance: LOC-questions, LOC-commands, visual fields, motor left arm, motor right arm, motor left leg, motor right leg; seven categories had moderate agreement: LOC-consciousness, best gaze, facial palsy, sensory, best language, dysarthria, extinction/inattention; one category had poor agreement: ataxia. There was high physician satisfaction with the device. The VNs rated 96% of the assessments as good or very good for "image quality," "sound quality," "ease of use," and "ability to assess subject using NIHSS," and 84% of the assesssments as good or very good for "reception in hospital." The smartphones with HQ-VTC is reliable, easy to use, and affordable for telestroke NIHSS administration. This device has high physician satisfaction. With the variety of smartphones and professional medical applications available today, the telestroke practitioner has all the tools necessary for fast clinical decision-makingby accessing electronic medial records, viewing images, and tracking patient vitals.
ContributorsVegunta, Sravanthi (Author) / Demaerschalk, Bart (Thesis director) / Santello, Marco (Committee member) / Hurlbut, Ben (Committee member) / Barrett, The Honors College (Contributor)
Created2012-05
Description
The purpose of this paper was to systematically review current literature regarding the effect of hand splints on aesthetic outcomes for individuals with acquired hand deformities. Hand splints vary in form and function, and are used to maintain or ameliorate hand function and aesthetics. A literature search was performed on peer-reviewed publications that used splinting as an intervention for conservative hand improvement. Evidence from ten randomized clinical trials (published from 2003 to 2015) was evaluated for aesthetic improvement among a total of 659 subjects. Cosmetic outcomes were analyzed by a change in angle measurements, such as extensor lag, ulnar deviation, and passive and active range of motion. Of these ten studies, five focused on hand deformities caused by neurological impairment, while the other five measured those with musculoskeletal complications. Only two of the ten studies concluded that splinting could aesthetically improve the hands, and only one of these reporting statistical significance in its data. The data was not only limited in quantity, but was presented in heterogeneous formats. There was an extensive variation in measured outcomes, intervention protocols, follow-up times, and many other aspects of the studies; this dissimilarity led to difficulty in performing a systematic assessment. The majority of evidence concludes that splinting does not improve the appearance of deformities, however none directly investigated this measure. Therefore, further RCTs that include measurements of cosmetic traits are necessary to better quantify the effect of splinting for management of hand deformities. This review was the first of its kind to evaluate the correction of hand deformities using splints as an intervention.
ContributorsVale, Nicholas Marshall (Author) / Santello, Marco (Thesis director) / Skiba, Jeffry (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor, Contributor) / School of Biological and Health Systems Engineering (Contributor)
Created2017-05
Description
High throughput transcriptome data analysis like Single-cell Ribonucleic Acid sequencing (scRNA-seq) and Circular Ribonucleic Acid (circRNA) data have made significant breakthroughs, especially in cancer genomics. Analysis of transcriptome time series data is core in identifying time point(s) where drastic changes in gene transcription are associated with homeostatic to non-homeostatic cellular transition (tipping points). In Chapter 2 of this dissertation, I present a novel cell-type specific and co-expression-based tipping point detection method to identify target gene (TG) versus transcription factor (TF) pairs whose differential co-expression across time points drive biological changes in different cell types and the time point when these changes are observed. This method was applied to scRNA-seq data sets from a SARS-CoV-2 study (18 time points), a human cerebellum development study (9 time points), and a lung injury study (18 time points). Similarly, leveraging transcriptome data across treatment time points, I developed methodologies to identify treatment-induced and cell-type specific differentially co-expressed pairs (DCEPs). In part one of Chapter 3, I presented a pipeline that used a series of statistical tests to detect DCEPs. This method was applied to scRNA-seq data of patients with non-small cell lung cancer (NSCLC) sequenced across cancer treatment times. However, this pipeline does not account for correlations among multiple single cells from the same sample and correlations among multiple samples from the same patient. In Part 2 of Chapter 3, I presented a solution to this problem using a mixed-effect model. In Chapter 4, I present a summary of my work that focused on the cross-species analysis of circRNA transcriptome time series data. I compared circRNA profiles in neonatal pig and mouse hearts, identified orthologous circRNAs, and discussed regulation mechanisms of cardiomyocyte proliferation and myocardial regeneration conserved between mouse and pig at different time points.
ContributorsNyarige, Verah Mocheche (Author) / Liu, Li (Thesis advisor) / Wang, Junwen (Thesis advisor) / Dinu, Valentin (Committee member) / Arizona State University (Publisher)
Created2022
Description
Beta-Amyloid(Aβ) plaques and tau protein tangles in the brain are now widely recognized as the defining hallmarks of Alzheimer’s disease (AD), followed by structural atrophy detectable on brain magnetic resonance imaging (MRI) scans. However, current methods to detect Aβ/tau pathology are either invasive (lumbar puncture) or quite costly and not widely available (positron emission tomography (PET)). And one of the particular neurodegenerative regions is the hippocampus to which the influence of Aβ/tau on has been one of the research projects focuses in the AD pathophysiological progress.
In this dissertation, I proposed three novel machine learning and statistical models to examine subtle aspects of the hippocampal morphometry from MRI that are associated with Aβ /tau burden in the brain, measured using PET images. The first model is a novel unsupervised feature reduction model to generate a low-dimensional representation of hippocampal morphometry for each individual subject, which has superior performance in predicting Aβ/tau burden in the brain. The second one is an efficient federated group lasso model to identify the hippocampal subregions where atrophy is strongly associated with abnormal Aβ/Tau. The last one is a federated model for imaging genetics, which can identify genetic and transcriptomic influences on hippocampal morphometry. Finally, I stated the results of these three models that have been published or submitted to peer-reviewed conferences and journals.
ContributorsWu, Jianfeng (Author) / Wang, Yalin (Thesis advisor) / Li, Baoxin (Committee member) / Liang, Jianming (Committee member) / Wang, Junwen (Committee member) / Wu, Teresa (Committee member) / Arizona State University (Publisher)
Created2022
Description
Although previous studies have elucidated the role of position feedback in the regulation of movement, the specific contribution of Golgi tendon organs (GTO) in force feedback, especially in stabilizing voluntary limb movements, has remained theoretical due to limitations in experimental techniques. This study aims to establish force feedback regulation mediated by GTO afferent signals in two phases. The first phase of this study consisted of simulations using a neuromusculoskeletal model of the monoarticular elbow flexor (MEF) muscle group, assess the impact of force feedback in maintaining steady state interaction forces against variable environmental stiffness. Three models were trained to accurately reach an interaction force of 40N, 50N and 60N respectively, using a fixed stiffness level. Next, the environment stiffness was switched between untrained levels for open loop (OL) and closed loop (CL) variants of the same model. Results showed that compared to OL, CL showed decreased force deviations by 10.43%, 12.11% and 13.02% for each of the models. Most importantly, it is also observed that in the absence of force feedback, environment stiffness is found to have an effect on the interaction force. In the second phase, human subjects were engaged in experiments utilizing an instrumented elbow exoskeleton that applied loads to the MEF muscle group, closely mimicking the simulation conditions. The experiments consisted of reference, blind and catch trial types, and 3 stiffness levels. Subjects were first trained to reach for a predetermined target force. During catch trials, stiffness levels were randomized between reaches. Responses obtained from these experiments showed that subjects were able to regulate forces with no significant effects of trial type or stiffness level. Since experimental results align closely with that of closed loop model simulations, the presence of force feedback mechanisms mediated by GTO within the human neuromuscular system is established. This study not only unveils the critical involvement of GTO in force feedback but also emphasizes the importance of understanding these mechanisms for developing advanced neuroprosthetics and rehabilitation strategies, shedding light on the intricate interplay between sensory inputs and motor responses in human proprioception.
ContributorsAbishek, Kevin (Author) / Lee, Hyunglae (Thesis advisor) / Buneo, Christopher (Committee member) / Santello, Marco (Committee member) / Arizona State University (Publisher)
Created2023