Matching Items (62)

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High-Intensity Exercise Preconditioning Prevents Downregulation of eNOS Expression in the Aorta Following Doxorubicin Treatment

Description

The anthracycline drug Doxorubicin (DOX) is a highly effective treatment for breast cancer, but its clinical utility is limited by dose-dependent cardiovascular toxicity. The toxic effects are partly attributed to

The anthracycline drug Doxorubicin (DOX) is a highly effective treatment for breast cancer, but its clinical utility is limited by dose-dependent cardiovascular toxicity. The toxic effects are partly attributed to DOX-induced generation of reactive oxygen species, which may impair nitric oxide-mediated vasodilation. Exercise training activates antioxidant defense mechanisms and is thus hypothesized to counteract oxidative stress when initiated prior to DOX administration. Adult 8-week old, ovariectomized female Sprague-Dawley rats were divided into 4 groups: sedentary + vehicle (Sed+Veh); Sed+DOX; exercise + veh (Ex+Veh); and Ex+DOX. Rats in the exercise groups were preconditioned with high intensity interval training consisting of 4x4 minute bouts of exercise at 85-95% of VO2peak separated by 2 minutes of active recovery performed 5 days per week. Exercise was implemented one week prior to the first injection and continued throughout the study. Animals received either DOX (4mg/kg) or veh (saline) intraperitoneal injections bi-weekly for a cumulative dose of 12 mg/kg per animal. Five days following the final injection, animals were anesthetized with isoflurane, decapitated and aortas and perivascular adipose tissue (PVAT) were removed for western blot analyses. No significant differences in aortic protein expression were detected for inducible nitric oxide synthase (iNOS) or the upstream activator of endothelial nitric oxide synthase (eNOS), Akt, across groups (p>0.05), whereas eNOS protein expression was significantly downregulated in Sed+DOX (p=0.003). In contrast, eNOS expression was not altered in Ex+DOX treated animals. Protein expression of iNOS in PVAT was upregulated with exercise in the DOX-treated groups (p=0.039). These findings suggest that exercise preconditioning may help mitigate vascular effects of DOX by preventing downregulation of eNOS in the aorta.

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  • 2016-12

Physiological Feats of the Body: How We Adapt to Anaerobic Stress Podcast

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****Project Disclaimer: Unfortunately due to the COVID-19 outbreak during Spring 2020, ASU shut down in-person classes and campus facilities as means to prevent the spread of the virus. This meant

****Project Disclaimer: Unfortunately due to the COVID-19 outbreak during Spring 2020, ASU shut down in-person classes and campus facilities as means to prevent the spread of the virus. This meant though that a polished final podcast recording was unable to be made. Instead, a first-run, practice podcast recording that was recorded before the shut down is uploaded in its stead as a reference as to how the final was intended to sound and be produced. ****

Cellular hypertrophy is an anaerobically-based, adaptive process that mammalian skeletal muscle undergoes in response to damage resulting from unaccustomed force generation by the muscle. Hypertrophy allows for the muscle tissue to recover from the immediate injury and also to be rebuilt more capable of withstanding producing the same amount of force without injury, should it happen again. This means the end result of an adapted muscle is an overall more efficient tissue. The ability to regenerate after damage to the structure and function of the muscle tissue is a highly orchestrated event involving multiple steps and key events to occur. Most briefly, a mechanical load is attempted to be lifted but due to demanding a high amount of contractile force to lift, it causes microdamage to the structural and contractile elements of muscle fiber’s sarcomeres. In addition to an inflammatory response, satellite cells, as a part of a myogenic response, are activated to invade the fiber and then permanently reside inside to produce new proteins that will replace the damaged and necrotized proteins. This addition of cellular content, repeated over multiple times, results in the increased diameter of the fibers and manifests in the visual appearance of skeletal muscle hypertrophy. These steps have been listed off devoid of the contexts in which it takes for these to occur and will be addressed within this thesis.

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  • 2020-05

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Statistical Analyses of Octopus bimaculoides Morphology and Physiology

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Chapter 1: Functional Specialization and Arm Length in Octopus bimaculoides<br/>Although studies are limited, there is some evidence that octopuses use their arms for specialized functions. For example, in Octopus maya

Chapter 1: Functional Specialization and Arm Length in Octopus bimaculoides<br/>Although studies are limited, there is some evidence that octopuses use their arms for specialized functions. For example, in Octopus maya and O. vulgaris, the anterior arms are utilized more frequently for grasping and exploring (Lee, 1992; Byrne et al., 2006a), while posterior arms are more frequently utilized for crawling in O. vulgaris (Levy et al., 2015). In addition, O. vulgaris uses favored arms when retrieving food and making contact with a T-maze as dictated by their lateralized vision (Byrne, 2006b). O. vulgaris also demonstrates a preference for anterior arms when retrieving food from a Y-maze (Gutnick et. al. 2020). In Octopus bimaculoides bending and elongation were more frequent in anterior arms than posterior arms during reaching and grasping tasks, and right arms displayed deformation more frequently than left arms, with the exception of the hectocotylus (R3) in males (Kennedy et. al. 2020). Given these observed functional differences, the goal of this study was to determine if morphological differences exist between different octopus arm identities, coded as L1-L4 and R1-R4. In particular, the relationship between arm length and arm identity was analyzed statistically. The dataset included 111 intact arms from 22 wild-caught specimens of O. bimaculoides (11 male and 11 female). Simple linear regressions and an analysis of covariance were performed to test the relationship between arm length and a number of factors, including body mass, sex, anterior versus posterior location, and left versus the right side. Mass had a significant linear relationship with arm length and a one-way ANOVA demonstrated that arm identity is significantly correlated with arm length. Moreover, an analysis of covariance demonstrated that independent of mass, arm identity has a significant linear relationship with arm length. Despite an overall appearance of bilateral symmetry, arms of different identities do not have statistically equivalent lengths in O. bimaculoides. Furthermore, differences in arm length do not appear to be related to sex, anterior versus posterior location, or left or right side. These results call into question the existing practice of treating all arms as equivalent by either using a single-arm measurement as representative of all eight or calculating an average length and suggest that morphological analyses of specific arm identities may be more informative.<br/><br/>Chapter 2: Predicting and Analyzing Octopus bimaculoides Sensitivity to Global Anesthetic<br/>Although global anesthetic is widely used in human and veterinary medicine the mechanism and impact of global anesthetic is relatively poorly comprehended, even in well-studied mammalian models. Invertebrate anesthetic is even less understood. In order to evaluate factors that impact anesthetic effectiveness analyses were conducted on 22 wild-caught specimens of Octopus bimaculoides during 72 anesthetic events.Three machine learning models: regression tree, random forest, and generalized additive model were utilized to make predictions of the concentration of anesthetic (percent ethanol by volume) from 11 features and to determine feature importance in making those predictions. The fit of each model was analyzed on three criteria: correlation coefficient, mean squared error, and relative error. Feature importance was determined in a model-specific manner. Predictions from the best performing model, random forest, have a .82 correlation coefficient with experimental values. Feature importance suggests that temperature on arrival and cohabitation factors strongly influence predictions for anesthesia concentration. This likely indicates the transportation process was incurring stress on the animals and that cohabitation was also stressful for the typically solitary O. bimaculoides. This long-term stress could lead to a decline in the animal’s well-being and a lower necessary ethanol concentration (Horvath et al., 2013). This analysis provides information to improve the care of octopus in laboratory settings and furthers the understanding of the effects of global anesthetic in invertebrates, particularly one with a distributed nervous system.

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  • 2021-05

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Evaluating the genomic basis of oxygen-limited thermal tolerance in Drosophila melanogaster

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I am evaluating the genomic basis of a model of heat tolerance in which organisms succumb to warming when their demand for oxygen exceeds their supply. This model predicts that

I am evaluating the genomic basis of a model of heat tolerance in which organisms succumb to warming when their demand for oxygen exceeds their supply. This model predicts that tolerance of hypoxia should correlate genetically with tolerance of heat. To evaluate this prediction, I tested heat and hypoxia tolerance in several genetic lines of Drosophila melanogaster. I hypothesized that genotypes that can fly better at high temperatures are also able to fly well at hypoxia. Genotypes from the Drosophila Genetic Reference Panel (DGRP) were assessed for flight at hypoxia and normal temperature (12% O2 and 25°C) as well as normoxia and high temperature (21% O2 and 39°C). After testing 66 lines from the DGRP, the oxygen- and capacity-limited thermal tolerance theory is supported; hypoxia-resistant lines are more likely to be heat-resistant. This supports previous research, which suggested an interaction between the tolerance of the two environmental variables. I used this data to perform a genome-wide association study to find specific single-nucleotide polymorphisms associated with heat tolerance and hypoxia tolerance but found no specific genomic markers. Understanding factors that limit an organism’s stress tolerance as well as the regions of the genome that dictate this phenotype should enable us to predict how organisms may respond to the growing threat of climate change.

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  • 2020-05

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Cannabis: Cannabinoids, Physiology, and Receptor Evolution

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The Cannabis plant has historical roots with human beings. The plant produces compounds called cannabinoids, which are responsible for the physiological affects of Cannabis and make it a research candidate

The Cannabis plant has historical roots with human beings. The plant produces compounds called cannabinoids, which are responsible for the physiological affects of Cannabis and make it a research candidate for medicinal use. Analysis of the plant and its components will help build a better database that could be used to develop a complete roster of medicinal benefits. Research regarding the cellular protein receptors that bind the cannabinoids may not only help provide reasons explaining why the Cannabis plant could be medicinally relevant, but will also help explain how the receptors originated. The receptors may have been present in organisms before the present day Cannabis plant. So why would there be receptors that bind to cannabinoids? Searching for an endocannabinoid system could help explain the purpose of the cannabinoid receptors and their current structures in humans. Using genetic technologies we are able to take a closer look into the evolutionary history of cannabinoids and the receptors that bind them.

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  • 2014-05

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Octopus Transverse and Internal Longitudinal Arm Muscles in Relation to Fetching Movements

Description

Octopus arms employ a complex three dimensional array of musculature, called a
muscular hydrostat, which allows for nearly infinite degrees of freedom of movement without
the structure of a skeletal

Octopus arms employ a complex three dimensional array of musculature, called a
muscular hydrostat, which allows for nearly infinite degrees of freedom of movement without
the structure of a skeletal system. This study employed Magnetic Resonance Imaging with a
Gadoteridol-based contrast agent to image the octopus arm and view the internal tissues. Muscle
layering was mapped and area was measured using AMIRA image processing and the trends in
these layers at the proximal, middle, and distal portions of the arms were analyzed. A total of 39
arms from 6 specimens were scanned to give 112 total imaged sections (38 proximal, 37 middle,
37 distal), from which to ascertain and study the possible differences in musculature. The
images revealed significant increases in the internal longitudinal muscle layer percentages
between the proximal and middle, proximal and distal, and middle and distal sections of the
arms. These structural differences are hypothesized to be used for rapid retraction of the distal
segment when encountering predators or noxious stimuli. In contrast, a significant decrease in
the transverse muscle layer was found when comparing the same sections. These structural
differences are hypothesized to be a result of bending behaviors during retraction. Additionally,
the internal longitudinal layer was separately studied orally, toward the sucker, and aborally,
away from the sucker. The significant differences in oral and aboral internal longitudinal
musculature in proximal, middle, and distal sections is hypothesized to support the pseudo-joint
functionality displayed in octopus fetching behaviors. The results indicate that individual
octopus arm morphology is more unique than previously thought and supports that internal
structural differences exist to support behavioral functionality.

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Date Created
  • 2019-05

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Evaluation of an Organic Mineral Complex on the Development of Cardiovascular Disease Risk Following a 10-week High-Fat Diet

Description

According to the World Health Organization, obesity has nearly tripled since 1975 and forty-one million children under the age of 5 are overweight or obese (World Health Organization, 2018). Exercise

According to the World Health Organization, obesity has nearly tripled since 1975 and forty-one million children under the age of 5 are overweight or obese (World Health Organization, 2018). Exercise is a potential intervention to prevent obesity-induced cardiovascular complications as exercise training has been shown to aid nitric oxide (NO) production as well as preserving endothelial function in obese mice (Silva et al., 2016). A soil-derived organic mineral compound (OMC) has been shown to lower blood sugar in diabetic mice (Deneau et al., 2011). Prior research has shown that, while OMC did not prevent high fat diet (HFD)-induced increases in body fat in male Sprague-Dawley rats, it was effective at preventing HFD-induced impaired vasodilation (M. S. Crawford et al., 2019). Six-weeks of HFD has been shown to impair vasodilation through oxidative-stress mediated scavenging of NO as well as upregulation of inflammatory pathways including inducible nitric oxide synthase (iNOS) and cyclooxygenase (Karen L. Sweazea et al., 2010). Therefore, the aim of the present study was to determine whether OMC alters protein expression of iNOS and endothelial NOS (eNOS) in the vasculature of rats fed a control or HFD with and without OMC supplementation. Six-week old male Sprague-Dawley rats were fed either a standard chow diet (CHOW) or a HFD composed of 60% kcal from fat for 10 weeks. The rats were administered OMC at doses of 0 mg/mL (control), 0.6 mg/mL, or 3.0 mg/mL added to their drinking water. Following euthanasia with sodium pentobarbital (200 mg/kg, i.p.), mesenteric arteries and the surrounding perivascular adipose tissue were isolated and prepared for Western Blot analyses. Mesenteric arteries from HFD rats had more uncoupled eNOS (p = 0.006) and iNOS protein expression (p = 0.027) than rats fed the control diet. OMC was not effective at preventing the uncoupling of eNOS or increase in iNOS induced by HFD. Perivascular adipose tissue (PVAT) showed no significant difference in iNOS protein expression between diet or OMC treatment groups. These findings suggest that OMC is not likely working through the iNOS or eNOS pathways to improve vasodilation in these rats, but rather, appears to be working through another mechanism.

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Date Created
  • 2020

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Repetitive mild traumatic brain injury induces ventriculomegaly and cortical thinning in juvenile rats

Description

Traumatic brain injury (TBI) most frequently occurs in pediatric patients and remains a leading cause of childhood death and disability. Mild TBI (mTBI) accounts for 70-90% of all TBI cases,

Traumatic brain injury (TBI) most frequently occurs in pediatric patients and remains a leading cause of childhood death and disability. Mild TBI (mTBI) accounts for 70-90% of all TBI cases, yet its neuropathophysiology is still poorly understood. While a single mTBI injury can lead to persistent deficits, repeat injuries increase the severity and duration of both acute symptoms and long term deficits. In this study, to model pediatric repetitive mTBI (rmTBI) we subjected unrestrained juvenile animals (post-natal day 20) to repeat weight drop impact. Animals were anesthetized and subjected to sham or rmTBI once per day for 5 days. At 14 days post injury (PID), magnetic resonance imaging (MRI) revealed that rmTBI animals displayed marked cortical atrophy and ventriculomegaly. Specifically, the thickness of the cortex was reduced up to 46% beneath and the ventricles increased up to 970% beneath the impact zone. Immunostaining with the neuron specific marker NeuN revealed an overall loss of neurons within the motor cortex but no change in neuronal density. Examination of intrinsic and synaptic properties of layer II/III pyramidal neurons revealed no significant difference between sham and rmTBI animals at rest or under convulsant challenge with the potassium channel blocker, 4-Aminophyridine. Overall, our findings indicate that the neuropathological changes reported after pediatric rmTBI can be effectively modeled by repeat weight drop in juvenile animals. Developing a better understanding of how rmTBI alters the pediatric brain may help improve patient care and direct "return to game" decision making in adolescents.

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Date Created
  • 2014

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Towards a systems biology understanding of metabolic syndrome

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This dissertation investigates the condition of skeletal muscle insulin resistance using bioinformatics and computational biology approaches. Drawing from several studies and numerous data sources, I have attempted to uncover molecular

This dissertation investigates the condition of skeletal muscle insulin resistance using bioinformatics and computational biology approaches. Drawing from several studies and numerous data sources, I have attempted to uncover molecular mechanisms at multiple levels. From the detailed atomistic simulations of a single protein, to datamining approaches applied at the systems biology level, I provide new targets to explore for the research community. Furthermore I present a new online web resource that unifies various bioinformatics databases to enable discovery of relevant features in 3D protein structures.

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Date Created
  • 2013

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Building adaptive computational systems for physiological and biomedical data

Description

In recent years, machine learning and data mining technologies have received growing attention in several areas such as recommendation systems, natural language processing, speech and handwriting recognition, image processing and

In recent years, machine learning and data mining technologies have received growing attention in several areas such as recommendation systems, natural language processing, speech and handwriting recognition, image processing and biomedical domain. Many of these applications which deal with physiological and biomedical data require person specific or person adaptive systems. The greatest challenge in developing such systems is the subject-dependent data variations or subject-based variability in physiological and biomedical data, which leads to difference in data distributions making the task of modeling these data, using traditional machine learning algorithms, complex and challenging. As a result, despite the wide application of machine learning, efficient deployment of its principles to model real-world data is still a challenge. This dissertation addresses the problem of subject based variability in physiological and biomedical data and proposes person adaptive prediction models based on novel transfer and active learning algorithms, an emerging field in machine learning. One of the significant contributions of this dissertation is a person adaptive method, for early detection of muscle fatigue using Surface Electromyogram signals, based on a new multi-source transfer learning algorithm. This dissertation also proposes a subject-independent algorithm for grading the progression of muscle fatigue from 0 to 1 level in a test subject, during isometric or dynamic contractions, at real-time. Besides subject based variability, biomedical image data also varies due to variations in their imaging techniques, leading to distribution differences between the image databases. Hence a classifier learned on one database may perform poorly on the other database. Another significant contribution of this dissertation has been the design and development of an efficient biomedical image data annotation framework, based on a novel combination of transfer learning and a new batch-mode active learning method, capable of addressing the distribution differences across databases. The methodologies developed in this dissertation are relevant and applicable to a large set of computing problems where there is a high variation of data between subjects or sources, such as face detection, pose detection and speech recognition. From a broader perspective, these frameworks can be viewed as a first step towards design of automated adaptive systems for real world data.

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Date Created
  • 2013