Anatomy Commons^™

Novel Analysis Of The Sars-Cov-2 Genome To Identify Positive Evolutionary Selection In The Spike Protein Of Emerging Variants, Ulysses Ison

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This thesis tests the hypothesis that the spike protein of SARV-CoV-2 is under positive evolutionary selection. A consensus nucleotide sequence was generated for the most current SARS-CoV-2 variant, XBB1.5, by performing sequence alignments of recent isolates. The consensus nucleotide sequence was translated to obtain the amino acid sequence. The amino acid and nucleotide sequences were compared to the original Wuhan-hu-1 strain to identify mutations. Forty-three mutations were identified in the spike protein, and all but two changed the amino acid. The majority of mutations were found in the receptor binding domain of the spike protein, which is the region of …

An Examination Of The Role Of Adrenergic Receptor Stimulation In Mediating The Link Between Early-Life Stress And The Sensitization Of Neuroinflammatory-Based Depressive-Like Behavior In Isolated Guinea Pig Pups, Rachel Renate Kessler

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Early-life stress appears to sensitize neuroinflammatory signaling to increase later vulnerability for stress-related mental disorders. How stress initiates this process is unknown, but sympathetic nervous system activation during the early stress may be key. Isolated guinea pig pups display inflammatory-mediated depressive-like behavior and fever that sensitize on repeated isolation. We assessed whether sympathetic nervous system activity contributed to the sensitization process in guinea pig pups. In Experiment 1, the adrenergic agonist ephedrine, either alone or with cortisol, did not increase depressive-like behavior or fever during an initial isolation the following day. In Experiment 2, both depressive-like behavior and fever sensitized …

Characterization Of Inhbb, Heatr5a, & Cyp2s1 Expression In Dorsal Root Ganglia By In-Situ Hybridization, Joshua D. Krech

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Multiple studies have shown that gene expression changes occur in sensory neurons after peripheral nerve injury (PNI). These expression changes include many genes that are turned on specifically in response to injury, but much less is know about expression changes in stable genetic markers of particular sensory neuron populations. This study characterized the expression of three markers of proprioceptive neurons Inhbb, Heatr5a, Cyp2s1 in lumbar dorsal root ganglion (DRG) neurons in intact animals and after PNI. To perform these experiments, we subcloned segments of the coding sequences of these genes and generated DIG-labeled riboprobes. Control experiments demonstrated the validity of …

The Effect Of Endogenous Ligands Of The Aryl Hydrocarbon Receptor On Antibody Expression In A Human B-Cell Model, Valerie Benedict

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Small changes in antibody expression have broad impacts on human health and disease. An environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces profound immune suppression in animal models in an aryl hydrocarbon receptor (AhR)-mediated fashion. In a human Burkitt's lymphoma cell line (CL-01), TCDD inhibited IgG secretion and differentially impacted Ig heavy chain expression. In addition to TCDD, the AhR has several endogenous, dietary, and bacterial ligands such as 6-formylindolo[3,2-b]carbazole (FICZ) and indole, which are present within the human body at varied concentrations (0.30 mM- 6.64 mM). Both FICZ (100 nM) and indole (100 µM) significantly reduced IgG secretion. Overall antibody secretion is …

Using Fmri Bold Imaging To Motion-Correct Associated, Simultaneously Imaged Pet Data, Joseph M. Williamitis

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Because magnetic resonance (MR) and positron emission tomography (PET) scanning sessions last long durations, motion blur during scanning constitutes a problem for clinical interpretation. To counteract this, motion-correction algorithms have been developed to reduce smearing between scan slices of MRI, but these algorithms are not commonplace for PET. This feasibility study determined if applying MRI motion-correction algorithms to simultaneously acquired PET data improved PET signal clarity in specific brain regions. Seven subjects received increasing levels of PET tracers while undergoing two separate simultaneous PET/MRI scans. We modified existing fMRI algorithms to apply them to the accompanying PET data. We hypothesized …

Using Functionalized Benzylidene Oxindoles To Determine An Improved Monoamine Oxidase-B Inhibitor As A Therapeutic Agent For Parkinson's Disease, Christine Morgan Kinstedt

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With the intent to create an optimized monoamine oxidase-B (MAO-B) inhibitor, researchers in this investigation synthesized derivatives of the benzylidene oxindole scaffold in order to determine a lead molecule for further drug development. Previous work in this laboratory group evaluated a similar scaffold, the chalcone structural unit. As this class of compounds was determined to possess the ability to permeate the blood brain barrier (BBB) and to act as potent MAO-B inhibitors, it was posited that scaffold hopping from this previously studied molecular skeleton to benzylidene oxindoles would provide analogous results. Benzylidene oxindoles are readily synthesized via the Claisen-Schmidt condensation …

Investigating The Effects Of Cyppa On Small-Conductance Calcium-Activated Potassium Channels In Sod1g93a Transgenic Mouse Model, Matthew M. Murphy

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Amyotrophic Lateral Sclerosis is a fatal, progressive, neurodegenerative disease. There currently is no cure for the disease and limited treatment options have modest effects. A hallmark of the disease is motoneuron degeneration. Within the membrane of motoneurons are small-conductance calcium-activated potassium channels. SK Channels function to mediate medium afterhyperpolarization period of an action potential and have substantial influence on the firing rate of motoneurons. SK channels, specifically SK2 and SK3 isoforms, have been shown through immunohistochemistry to be affected in the SOD1G93A mouse model. The goal of this study was to investigate whether neonatal administration of CyPPA, a potent SK2 …

Characterization Of B3galt2 And Heg1 Expression In Dorsal Root Ganglia, Alexander H. Nguyen

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Proprioception provides unique sensory feedback about the body’s orientation in space and this sensation is essential for creating specific motor functions and coordinated movement. During neurogenesis, unique genetic markers are expressed and classified as early, transient/middle, and late markers depending on their timing of expression. This study focuses on the expression patterns of two late markers: Heg1 and B3galt2. We investigated how expression of these two markers respond to peripheral nerve injury (PNI). We cloned and generated riboprobes to detect expression of B3galt2 and Heg1 in DRGs using in situ hybridization after transection of the sciatic nerve. B3galt2 hybridization in …

The Role Of Igf-1 In Geriatric Skin, Amber Castellanos

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Keratinocytes are cells that largely occupy the epidermis layer of our skin and function to protect against DNA damage induced by ultraviolet radiation. Keratinocytes rely on the activation of the IGF-1 receptor in order to carry out an appropriate response to UV-B radiation. Keratinocytes themselves do not express the IGF-1 ligand; IGF-1 is produced by fibroblasts found in the dermis layer of the skin. With age, fibroblasts become senescent and this interferes with their ability to produce IGF-1 for the epidermal IGF-1R. This occurrence may aid in understanding why geriatric individuals are at greatest risk for developing nonmelanoma skin cancers, …

Impact Of Passive Range Of Motion Exercises And Stretching In Knee Osteoarthritis Pain During Walking, Dominique Marchelle Ottonello

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Knee osteoarthritis (KOA), is globally prevalent source of disability for the elderly. This degenerative malady progresses with age and has no cure. It manifests in gait changes and affects overall quality of life. Exercise therapy has been shown to improve knee joint range of motion, stiffness and pain due to KOA. This improvement is due in part to the direct relationship between muscle strength and joint stability. The purpose of this study is to examine how a passive range of motion (ROM) exercises and stretching regimens affect gait-alterations and associated pain from KOA experienced during walking. Nine KOA subjects were …

Determining Effects Of The Paf-R And Anti-Hypertensive Drugs Mediated Microvesicle Particle Release In Modulating Anti-Tumor Response Of Lung Cancer, Andrew Stephen Forino

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Lung cancer is one of the world’s leading causes of cancer-related deaths with poor prognosis, and difficult to treat malignancy. Several genetic, and environmental factors including cigarette smoking and hypertension have been linked as the common risk factors for lung cancer. To that end, multiple mechanisms have been proposed in regulating tumor growth, angiogenesis, and metastasis, as well as the efficacy of cancer therapy in experimental lung cancer models. Importantly, studies including ours, have shown that exposure to reactive oxygen species (ROS)-generating stimuli such as cigarette smoking, and cancer therapy produced oxidized lipids with platelet-activating factor (PAF) agonistic activity from …

Discovery And Characterization Of Pathways Involved In Fus And Tdp43-Induced Toxicity In Yeast, Weston Joseph Shaw

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High-throughput genome-scale studies are becoming increasingly common as a means to discover genetic interactions. This methodology is particularly efficient when performed in the budding yeast Saccharomyces cerevisiae. Here, we (1) overexpress a large human gene library in yeast to assess how many of them are toxic, and (2) use the list of genes generated above to refine and analyze human genes previously identified to enhance toxicity of two ALS-associated proteins, FUS and TDP-43. By introducing each of 13,500 human genes into yeast, we demonstrated that the majority of these genes (about 97%) are not toxic to yeast when overexpressed. These …

Social Buffering By Unfamiliar Adult Males In Periadolescent Guinea Pigs: The Effects On Hpa Axis Activity And Fos Induction In The Medial Prefrontal Cortex, Alexander Bertke

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In the guinea pig, the ability of the mother’s presence to buffer hypothalamic-pituitary- adrenal (HPA) axis activation in her young during exposure to stressful stimuli has been well documented. Under similar testing conditions, other conspecifics (littermates, other adult females) are less effective in doing so. The effect does seem to wane with age but is still present to a significant degree in offspring approaching adolescence. However, we recently observed that an unfamiliar adult male buffered HPA axis activation and increased Fos expression in the prefrontal cortex of preweaning infants exposed to a novel enclosure at both 60 and 120 minutes …

Assessment Of Pseudo-Continuous Arterial Spin Labeling (Pcasl) Inter-Session Reliability In The Quantification Of Cerebral Perfusion, Mohammad Ahmad Awad

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Arterial spin labeling (ASL) is a magnetic resonance imaging (MRI) technique used for measuring cerebral blood flow (CBF) in a completely non-ionizing and non invasive fashion. ASL is useful in perfusion studies on healthy adult & pediatric subjects, individuals who need multiple follow-ups, and patients with varying cerebrovascular diseases where changes in CBF can be used as an indicator of tissue viability. We used a variation of the ASL technique known as pseudo-continuous ASL (pCASL). This form of ASL is the clinical standard (Alsop et al., 2015). However, it is not well documented the that pCASL is reliable between sessions …

Effect Of Hybrid/Complex N-Glycosylation On Cardiac Voltage-Gated Ion Channel Expression, Austin R. Parrish

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Dilated cardiomyopathy (DCM) is one the most common forms of heart failure, with the majority of cases being idiopathic. Dr. Bennett’s laboratory previously showed that deletion of the Mgat1 gene in cardiomyocytes only (Mgat1KO) is sufficient to cause DCM leading to heart failure and early death. The Mgat1 gene product, GlcNAcT1, is responsible for initiating the formation of hybrid/complex N-glycosylation. These data suggest a link between abnormal glycosylation and heart disease; however, there is a mystery of how the specific changes in glycosylation contribute to heart disease etiology and progression. The proper function and gating of voltage-gated Na+ channels (Nav) …

Calpain-Calpastatin System In Peripheral Nerve Myelination And Demyelination, Domenica Elizabeth Drouet Saltos

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Myelin is the structure formed by glial cells that electrically insulates axons aiding in propagation of action potentials. Disruption of myelin sheath (demyelination) is common to neurological diseases, such as multiple sclerosis (MS). The calcium-dependent protease, calpain, is known to modulate myelination during central nervous system (CNS) development. Endogenous calpain inhibitor, calpastatin, regulates calpain activity. The calpain-calpastatin system has been implicated in the CNS demyelination occurring in diseases. Charcot-Marie-Tooth disease (CMT) is a hereditary demyelinating polyneuropathy affecting proper functioning of peripheral nerves, demonstrating the importance of myelin in the peripheral nervous system (PNS). However, calpain’s role in the mechanism(s) of …

Calcium Imaging Of Developing Proprioceptive Dorsal Root Ganglion Neurons, Kaitlyn Louise Parkes

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Proprioception is an important sensation capable due to proprioceptive sensory neuron afferents found in muscles in the periphery being processed by the central nervous system. The nervous system is a complex system that continues to develop and mature as an animal ages. Much is not known of proprioceptive neurons and how they develop with time. Calcium is an important molecule in maintaining action potentials and homeostasis in neurons which can be studied to understand a variety of things about a neuron. This study uses genetically encoded calcium indicators to tag parvalbumin positive cells in the dorsal root ganglion (DRG) in …

The Influence Of Static Stretching Of Knee Flexors On Knee Biomechanics, Joshua David Perrin

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There is a greater incidence of non-contact anterior cruciate ligament (ACL) injury in female athletes compared to males. The higher rate of ACL injury in female athletes is most likely multifactorial and is influenced by intrinsic and extrinsic risk factors. This study examines the effects of an extrinsic factor — static stretching of the hamstrings on knee biomechanics. Twelve female athletes performed drop vertical jump (DVJ) tasks before and after a hamstrings static stretching protocol. Knee kinematics and kinetics were recorded during the contact phase of the DVJ. The results of this study revealed stretching had no significant effect on …

The Effect Of Soleus Fatigue During Sidestep Cutting Maneuvers: Implications For The Acl, Michael William Ciesa

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The soleus muscle is a monoarticular plantarflexor composed slow-twitch fatigue-resistant muscle fibers. Through its attachment to the proximal tibia, contraction of the soleus muscle in a closed kinetic chain (when the foot is planted) produces a posterior pulling force on the posterior proximal tibia. The anterior cruciate ligament (ACL) is responsible for preventing anterior displacement of the tibia relative to the femur. Through the production of a posterior pulling force on the tibia, soleus muscle contraction in a closed kinetic chain could help reduce strain on the ACL. Fatigue is a neuromuscular phenomenon that can alter biomechanical strategies during athletics …

Exploring Gender Differences Throughout Normal Rat Aging - A Role For Estrogen Signaling In The Brain, Christopher Mark Evola

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Females are more protected than males from neurodegenerative diseases until they go through menopause when this protection drops dramatically. It has been hypothesized that this neuroprotection is hormone-dependent. The current study characterized cell signaling molecules downstream of estrogen receptor beta that are known to play a role in memory, PKC, ERK, and connexin-43, in regions of the brain associated with memory decline in an attempt to elucidate significant changes that occur post-estrus. Total whole cell lysates were compared to isolated mitochondrial protein because mitochondrial function is known to be altered during aging. As hypothesized, protein concentrations differed depending on age, …

Effects Of Abstraction And Assumptions On Modeling Motoneuron Pool Output, John Michael Allen

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Computational modeling has long been used in neuroscience as a supplement to more traditional experimental techniques, as it provides some advantages in terms of the level and detail of control available over the system being studied. At the same time, modeling has significant disadvantages by virtue of adding additional uncertainty to results and forcing the definition of potentially unclear physiological mechanisms. Nevertheless, modeling can provide useful insights when carefully defined and constrained. In this thesis, a model of the a-MN pool innervating the cat medial gastrocnemius was constructed. This model was then used to address two major questions, one regarding …

Analysis Of Stretch Reflex Responses In Mice Lacking Munc18-1 In Proprioceptors, Amr Mohi

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The monosynaptic stretch reflex circuit is one of the simplest circuits of the central nervous system. We studied the connection between Ia proprioceptive afferents and motor neurons that comprise the circuit, by stimulating the dorsal root and recording from the ventral root of the fourth lumbar spinal nerve. In our study, we analyzed the status of neurotransmission in the stretch reflex circuit in postnatal PV-cre; munc18-1 lox/lox conditional mutant mice. Munc18-1 is responsible for synaptic vesicular release in neurons. In the PV-cre; Munc18-1 lox/lox mutants we use, Munc18-1 is only knocked out in proprioceptive afferents and A-beta somatosensory afferents, both …

The Influence Of Age At Menarche And Hamstrings Fatigue On Knee Biomechanics, Stephanie Eileen Field

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Anterior cruciate ligament (ACL) injury is 4-8 times more likely to occur in females than in males and is associated with significant morbidity. The mechanism underlying the gender disparity in non-contact ACL injuries is likely multifactorial, and may be influenced by a variety of risk factors. This study examines the influence of age at menarche and neuromuscular fatigue of the hamstrings muscles on knee biomechanics. Twelve female athletes performed drop vertical jump (DVJ) tasks before and after a fatiguing protocol utilizing a glute-ham bench. Knee kinematics and kinetics were recorded during the contact phase of the DVJ. The results of …

Translocation And Phosphorylation Of Ampa Receptors Following Transcranial Direct Current Stimulation In Vivo, Justin Andrew Stafford

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Transcranial direct current stimulation (tDCS) is the current technique used clinically to attenuate the effects of various neurological related deficits and augment functions such as memory and learning. The cellular and molecular mechanisms behind tDCS remain largely unknown and this study provides some of the first insights into the mechanisms behind tDCS. Direct current stimulation has been used to increase levels of long term potentiation (LTP) ex vivo suggesting that this stimulation has an effect on the LTP mechanisms of action. Subcellular protein extraction and fractionation methods were used to isolate synaptoneurosomes from various brain regions to assess the effects …

The Timing Of Fluoxetine, Simvastatin And Ascorbic Acid Administration In A Post-Ischemic Stroke Environment Affects Infarct Volume And Hemorrhagic Transformation Frequency, Neal R. Verma

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Previous animal experiments have indicated that administration of fluoxetine and simvastatin at 20-26 hours post-stroke decreases the volume of ischemic infarcts. This experiment expanded on previous experiments by adding ascorbic acid to the post-stroke regimen, initiating simvastatin pre-stroke, and adding a third initiation time frame (48-54 hours). Male retired breeder Sprague-Dawley rats were on simvastatin for 7 days prior to stroke induction. Combined medications of 5 milligrams/kilogram of fluoxetine, 1 milligram/kilogram of simvastatin and 20 milligrams/kilogram of ascorbic acid were orally administered at 6-12 hours, 20-26 hours, or 48-54 hours, respectively, following stroke induction. Adult rats that were treated 20-26 …

The Inhibitory Effects Of Opioids On Voltage-Gated Calcium Influx In Neonatal Rat Carotid Body Type I Cells, Ellen M. Ricker

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It is known that opioids inhibit the hypoxic ventilatory response, but little is known about the mechanisms that underpin this. This study's objectives were to examine which opioid receptors are located on the oxygen-sensing carotid body type I cells and determine whether selective agonists inhibit cellular excitability.

Immunocytochemistry revealed the presence of μ and κ opioid receptors on type I cells. The μ-selective agonist DAMGO (10μM) and the κ-selective agonist U50-488 (10μM) significantly (p<0.0025 and p<0.0095 respectively, unpaired student's t-test) inhibited high K+ induced rises in intracellular Ca2+ compared with controls. After a three-hour incubation with pertussis toxin, a Gi protein-coupled inhibitor, DAMGO and U50-488 (10μM) has no significant effect on the responses to K+.

These results indicate that opioids acting at μ and κ receptors inhibit voltage-gated Ca2+ influx in carotid body type I cells. This mechanism may explain, in …

Angiotensin-Ii Receptor Blocker And Its Effects On Depressive-Like Behavior During Maternal Separation, Evan D. Xanthos

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Maternal separation has been shown to promote the onset of adult depression. This early life stressor produces a biphasic response marked by an active "protest" phase followed by a passive "despair" phase in humans and other species. In infant guinea pigs, active phase behaviors include increased locomotion and distress vocalizations, whereas the passive phase is marked by depressive-like behaviors including a crouch stance, eye closure and piloerection. Separation elicits physiological responses including increased core body temperature and proinflammatory cytokine expression suggesting fever. Angiotensin-II receptor blockers (ARB's) inhibit inflammation both peripherally and centrally following peripheral administration. The goal of the present …

Is Polyvinylidene Diflouride (Pvdf) Film Biocompatible In The Murine Cochlea?, Robert Maxwell Jaggers

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Polyvinylidene fluoride (PVDF) film, a biomaterial that is an integral part of a Totally Implantable Sustainable Hearing Aide (TISHA) device, was examined to determine its biocompatibility within the murine cochlea. The biofilm was implanted in the ear using a round window cochleostomy in 7-9 week old male C57BL/6 mice. Three test groups containing seven mice each were implanted with PVDF film. Each mouse received a sham surgery on the non-implanted cochlea. Three test groups were examined at 48 hours, 3 weeks, and 3 months. At the end of this time the mouse was euthanized, the tissue containing the cochlea was …

Efficacy Of Mastery-Based And Autonomy-Supportive Neuroanatomy Curriculum In Graduate Level Human Neurobiology Course, Corin Wolfgang Magee

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Anatomy provides scientists with a common vocabulary for discussing the human body, and is, therefore, an important aspect of science education. Literature shows that traditional teaching methods may be enhanced by the employment of mastery-based learning in an autonomy-supportive environment. The present study sought to determine the effects of these teaching strategies on the learning of neuroanatomy in a graduate neurobiology course.

These results show students learned and reportedly enjoyed learning a large amount of neuroanatomy. Experimentally taught students who completed the curriculum did well on the 30-item neuroanatomy quiz (mean score 81%), which was administered at the end of …

Mechanisms Of Hyperglycemia-Induced Ros Production In Osmotically Swollen Glial Cells, Augusta K. Eduafo

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Cerebral edema is a potentially fatal complication of diabetes. There is evidence for increased Reactive Oxidative Species (ROS) production during cerebral edema in diabetics. This can lead to oxidative stress, thought to contribute to the onset and progression of diabetes and can cause cell injury and cell death. ROS, in moderate amounts, are involved in physiological processes within the body that produce favorable cellular responses. Unfortunately, high levels of ROS can lead to cellular damage of lipids, membranes, proteins and DNA. Hyperglycemia can cause an increase in ROS production due to activation of NADPH oxidases. The purpose of this study …