Physiology Commons^™

Comparative Analysis Of Longevity And Stress Resiliency Benefits Of Supplementation With High-Antioxidative Capacity Juices In Organisms That Are Representative Of Humans, Meghan Long

Honors Scholar Theses

Neurodegenerative disease presents itself in a complex array of illnesses that is increasingly affecting the geriatric population. There has not been research on a common cause since there are a culmination of reasons that are probable ranging from genetic to environmental factors. Antioxidants have been known to prevent and protect against the damage that is otherwise caused by reactive oxygen species (ROS). Thus, high-capacity antioxidant juices supplemented into the diet of animal models such as Caenorhabditis elegans, Drosophila melanogaster, rats, and humans will allow for the study of the possible benefits.

Although a conclusion and common causation on the usage …

Synphilin-1 And Its Effects On Pathogenesis Of Parkinson’S Disease, Mirghani Mohamed

Honors Scholar Theses

Parkinson's Disease (PD) is a progressive neurodegenerative and movement disorder primarily caused by the degradation of dopaminergic neurons. Known markers of neurodegeneration in PD are Lewy Bodies, which are fibrillar aggregates that are found in the brains of PD patients. Lewy Bodies can accumulate from specific mutations in the SNCA gene that codes for alpha-synuclein, a protein enriched in presynaptic neurons. A mutated SNCA gene can cause conformational aggregates of alpha-synuclein to form toxic species mediating neuronal death. Research into alpha-synuclein has led to the discovery of a binding partner known as synphilin-1 that is also found in protein aggregates …

Identifying The Cell Composition And Clonal Diversity Of Supratentorial Ependymoma Using Single Cell Rna-Sequencing, James He

University Scholar Projects

Ependymoma is a primary solid tumor of the central nervous system. Supratentorial ependymoma (ST-EPN), a subtype of ependymomas, is driven by an oncogenic fusion between the ZFTA and RELA genes in 70% of cases. We introduced this fusion into neural progenitor cells of mice embryos via in utero electroporation of a non-viral binary piggyBac transposon system containing ZFTA-RELA. From preliminary data in the LoTurco lab, inducing the expression of ZFTA-RELA into different neural progenitor cells produces tumors of varying lethality and cellular composition. To define the cellular composition and subclonal diversity of ST-EPN tumors, we used single cell RNA-sequencing to …

Identifying The Cell Composition And Clonal Diversity Of Supratentorial Ependymoma Using Single Cell Rna-Sequencing, James He

Honors Scholar Theses

Ependymoma is a primary solid tumor of the central nervous system. Supratentorial ependymoma (ST-EPN), a subtype of ependymomas, is driven by an oncogenic fusion between the ZFTA and RELA genes in 70% of cases. We introduced this fusion into neural progenitor cells of mice embryos via in utero electroporation of a non-viral binary piggyBac transposon system containing ZFTA-RELA. From preliminary data in the LoTurco lab, inducing the expression of ZFTA-RELA into different neural progenitor cells produces tumors of varying lethality and cellular composition. To define the cellular composition and subclonal diversity of ST-EPN tumors, we used single cell RNA-sequencing …

Mechanisms Of Statin Effects On Muscle And Neuronal Proteostasis, Daniel Yu

University Scholar Projects

Statins are widely prescribed and used chronically, but we know little about the effects on long-term protein homeostasis during stress and aging. Our aim was to quantify the effect of statins on stress-induced protein damage. We administered atorvastatin in a dose-response curve in Caenorhabditis elegans under naïve control conditions and in conditions of hypertonic and heat stress known to induce muscle damage measurable as countable puncta in a polyglutamine aggregation model of damage. We observed that there is significant polyglutamine aggregation variability among worms at baseline and thus further study requires within experiment baseline controls, per worm. Our results are …

Microglia-Neuron Interactions In A Mouse Model Of Low Grade Neuroepithelial Tumors, Veolette Hanna

Honors Scholar Theses

Microglia are the macrophages of the brain and spinal cord, playing an important role in the immune response to disease states of the nervous system. This study conducts an investigation on the activity of microglia in response to low grade neuroepithelial tumors. Using mouse models and microglial markers, a qualitative and quantitative analysis of microglia activation, migration, and invasion within the brain cortex during early stages of tumor development was conducted. It was found that the presence of a low grade neuroepithelial tumor in the cortex of one hemisphere of the brain causes significant microglia activation in comparison to the …

Amygdala And Neocortical Structural Volume Analysis In The Shank3b Mutant Mouse Model Of Autism Spectrum Disorder, Preet Sawhney

Honors Scholar Theses

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that is characterized by abnormal social behavior, deficits in communication, and motor stereotypy. The SHANK3 gene, responsible for the generation of a scaffolding protein that is integral for the development of synapses, has been identified as one of the primary candidate genes implicated in the disorder. Shank3B is the rodent homolog for this gene. Research has shown that when this gene is disrupted in rodent models (e.g., via knock-out (KO)), ASD-like behaviors result. These include deficits in social interaction, increased anxiety, and repetitive self-grooming. The current study aimed to identify a physiological …

Assessing The Morphology Of Vesicles In Inhibitory Symmetric Synapses In Safety And Fear Conditions In The Rat Lateral Amygdala, Valerie Kress

Honors Scholar Theses

There is a significant lack of research on vesicle morphology in inhibitory synapses in the rat lateral amygdala. Published research focuses heavily on excitatory synapses in different parts of the rat brain and even this research rarely focuses on the different vesicle types in axons. It is reported that in these axons, synaptic vesicles traditionally contain neurotransmitters while small dense core vesicles contain active zone proteins and large dense core vesicles contain neuropeptides. This study aims to find correlations between vesicle morphology, location, contents, and potential function of each of the different types of vesicle in inhibitory axons.

After reviewing …

Development Of A Sonically Powered Biodegradable Nanogenerator For Bone Regeneration, Avi S. Patel

University Scholar Projects

Background: Reconstruction of bone fractures and defects remains a big challenge in orthopedic surgery. While regenerative engineering has advanced the field greatly using a combination of biomaterial scaffolds and stem cells, one matter of difficulty is inducing osteogenesis in these cells. Recent works have shown electricity’s ability to promote osteogenesis in stem cell lines when seeded in bone scaffolds; however, typical electrical stimulators are either (a) externally housed and require overcomplex percutaneous wires be connected to the implanted scaffold or (b) implanted non-degradable devices which contain toxic batteries and require invasive removal surgeries.

Objective: Here, we establish a biodegradable, piezoelectric …

Development Of A Sonically Powered Biodegradable Nanogenerator For Bone Regeneration, Avi Patel

Honors Scholar Theses

Background: Reconstruction of bone fractures and defects remains a big challenge in orthopedic surgery. While regenerative engineering has advanced the field greatly using a combination of biomaterial scaffolds and stem cells, one matter of difficulty is inducing osteogenesis in these cells. Recent works have shown electricity’s ability to promote osteogenesis in stem cell lines when seeded in bone scaffolds; however, typical electrical stimulators are either (a) externally housed and require overcomplex percutaneous wires be connected to the implanted scaffold or (b) implanted non-degradable devices which contain toxic batteries and require invasive removal surgeries.

Objective: Here, we establish a biodegradable, piezoelectric …

Embryonic Lethality Of Cranial Neural Crest Deletion Of Cdc73, Lilia Shen

Honors Scholar Theses

Hyperparathyroidism-jaw tumor (HPT-JT) syndrome is a disease characterized by parathyroid tumors, renal cysts or tumors, uterine tumors, and ossifying jaw fibromas. The cause of this syndrome is linked to a tumor suppressor gene called Cdc73, which encodes the protein product parafibromin. The loss of proper expression of Cdc73/parafibromin is implicated in the development of the tumors typical of HPT-JT, although the exact mechanisms of tumorigenesis are unclear. In particular, not much is understood about the development of ossifying fibromas (OF) of the jaw in this syndrome. OF is a benign bone neoplasm that can affect the mandible and …

Development And Ex Vivo Characterization Of Enteric Coated Chitosan Beads For Crohn’S Disease Management, Craig Mendonca

University Scholar Projects

Drug delivery is the process of transporting a drug to its site of action. It includes controlled delivery, where the drug is released at the tissue in a regulated manner. Additionally, it includes targeted delivery, where the drug is aimed at a specific tissue or region to avoid unwanted side effects (that would occur if the drug were distributed throughout the body). A cellulose acetate phthalate coated chitosan bead was developed as a formulation for controlled and targeted release of dexamethasone to the ilium and colon. This formulation was determined to be effective in delaying dexamethasone release until the formulation …

Pyruvate Kinase Isoform M2 Influences Autophagy And Related Processes In Hepatocellular Carcinoma Cells, Matthew Lin

University Scholar Projects

Hepatocellular carcinoma (HCC) is the most common form of liver cancer that affects ~14 million people in the world. Like all cancers, HCC is a disease that arises from unstinted cellular growth initiated by genetic alterations, metabolic changes, and dysregulation in key cellular pathways. Of interest is the relationship between metabolism and cell proliferation/degradation for therapeutic targeting. Pyruvate kinase M2 is a dimeric, glycolytically inactive isoform of the final enzyme involved in glycolysis, that is often upregulated in cancerous tissue. It is thought that the enzymatic function of PKM2 outside of glycolysis contributes to the biosynthesis of anabolic intermediates used …

Reconstitution Of Gabaergic Postsynapses In Host Cells, Karthik Kanamalla

Honors Scholar Theses

Type A GABA receptors (GABAARs) can be found embedded in postsynaptic membranes or in a variety of extrasynaptic locations. Receptors with synaptic function are recruited to the postsynapse by submembranous scaffolds composed of gephyrin and collybistin (CB). This study was aimed at assessing whether the ability to interact with the scaffold differentiates synaptic from non-synaptic receptors. Using HEK293 cells as an expression system, and indirect immunofluorescence (IF), co-localization of extrasynaptic receptors α1β3δ and α4β3δ with the CB-gephyrin scaffold was assessed and compared with that of the synaptic receptor α1β3γ2. Results indicated that both extrasynaptic receptors were able to colocalize with …

Exploring The Effect Of Novel Small Molecules On Oligodendrocyte Precursor Proliferation, Sagune Sakya

University Scholar Projects

Gliomas, a type of brain tumor, can be difficult to treat and have a poor survival rate. One pathway that leads to glioma formation is excessive signaling by platelet derived growth factors (PDGF) through PDGF receptor α (PDGFRα). Through this research, I found that novel compounds that downregulate PDGFRα decrease proliferation of Oli-neu cells, an oligodendrocyte precursor cell model, and identified signaling pathways through which these compounds may exert their effect. Further investigation may identify targets for development of glioma treatments.

Programming Heart Disease: Does Poor Maternal Nutrition Alter Expression Of Cardiac Markers Of Proliferation, Hypertrophy, And Fibrosis In Offspring?, Cathy Chun

Honors Scholar Theses

Maternal malnutrition can affect fetal organogenesis, metabolic processes, and factors involved in developmental regulation. Of the many physiological effects poor maternal nutrition can induce in offspring, one of the most important organs affected is the heart. Cardiovascular disease has been associated with poor maternal diet. It also been suggested that hypertension can originate during impaired intrauterine growth and development. Hypertension can trigger hypertensive heart disease and is associated with numerous heart complications. We hypothesized that poor maternal nutrition would alter critical growth factors associated with normal heart development, specifically, insulin-like growth factor (IGF)-1, IGF-2, transforming growth factor (TGF)β, and connective …

Development Of Vip-Sst Interneuron Associations In Mouse Neocortex And Entorhinal Cortex, Aayushi A. Mehta

Honors Scholar Theses

Cortical networks depend upon inhibition through the neurotransmitter GABA to control and coordinate specific spatiotemporal circuit patterns, underlying the exquisite complexity of neural signaling. Disinhibition, a form of inhibition where inhibitory neurons inhibit other inhibitory cells, further aids in amplifying local neural processing in a selective, organized manner. A subset of GABAergic interneurons, vasoactive intestinal peptide-expressing (VIP) cells, preferentially inhibit somatostatin interneurons, which provide inhibitory input onto pyramidal cells, thus creating an archetypal circuit illustrating disinhibition in the cortex. The aim of this anatomical study was to investigate variations in GABAergic VIP synapses onto somatostatin-expressing inhibitory interneurons in mice at …

Discovering The Sequence Specificity Of Human Dyrk2 And Dyrk4, Julie Klaric

University Scholar Projects

Protein phosphorylation is a post-translational modification (PTM) that is ubiquitous in regulating cellular processes. It is the most common PTM used in signal translation. Protein kinases are the class of enzymes that catalyze the transfer of a phosphate group from ATP to a specific amino acid on a substrate protein. In eukaryotes, kinases generally add a phosphate to serine, threonine, or tyrosine residues. Short linear patterns in the amino acid sequence of the substrate protein help guide the protein kinase to the correct residue to be phosphorylated. However, these patterns, or “motifs,” as well as the complete list of substrates …

Manipulation Of The Microbiome And Its Impact On Functional Recovery Following Ischemic Stroke, Michal Jandzinski

Honors Scholar Theses

Each year, nearly 800,000 individuals residing in the United States will have a stroke. Of these, about 130,000 cases will prove fatal while many of the survivors will be forced to live with disability for the remainder of their lives. Out of all strokes over 87% are ischemic strokes. The widespread incidence of this debilitating condition costs the United States an estimated $36.5 billion dollars every single year. Despite this, clinicians are armed with very little to combat the disease. Recent research developments have brought about the rise in awareness about the importance of the microbiome, the various gut flora …

Pathological Effects Of Repeated Concussive Tbi In Mouse Models: Periventricular Damage And Ventriculomegaly, Richard H. Wolferz Jr.

Honors Scholar Theses

Repeated concussive traumatic brain injury (rcTBI) is the most prominent form of head injury affecting the brain, with an estimated 1.7 million Americans affected each year (Kuhn 2012). Neurologists have been concerned about the danger of repeated head impacts since the 1920’s, but researchers have only begun to understand the long-term effects of rcTBI (McKee 2009). Although symptoms can be as mild as dizziness, current research suggests that multiple concussions can lead to a progressive degenerative brain disease known as chronic traumatic encephalopathy (CTE) (Luo 2008, McKee 2009, Kane 2013). Research on the brain is just beginning to scratch the …

The Development Of Skeletal Muscle In Young Horses: An Ultrasonography And Satellite Cell Approach, Emma K. Lavigne

Honors Scholar Theses

Muscle growth in young horses is characterized by an increase in muscle cross-sectional area, which can be accomplished through the activation and differentiation of satellite cells. Satellite cells can be stimulated or inhibited in response to different cytokines and growth factors and are key mediators of muscle hypertrophy and regeneration. The aim of this study was to investigate the growth of the longissimus dorsi (LD) muscle in horses under 5 years of age and to obtain preliminary data on satellite cell behavior in foals. The area, width, height, and subcutaneous fat were measured using ultrasonography at 6-month increments over the …

Direct Reprogramming Of Mouse Embryonic Fibroblasts Into Gabaergic Neurons, Nicholas J. Wasko

Honors Scholar Theses

Recent studies in which mouse and human fibroblasts were directly reprogrammed into functional neurons have demonstrated that lineage-specific transcription factors can override differentiation processes previously thought to be irreversible. Notably, three factors have been shown to be required for the induction of neural cell fate. Subsequent experiments have identified additional factors capable of generating specific neuronal subtypes, including motor neurons and dopaminergic neurons, but the factors necessary for inducing GABAergic neuronal fate have yet to be elucidated. Here, factors linked to GABAergic fate were transfected into mouse fibroblasts in order to identify candidate factors for inhibitory interneuron direct reprogramming. Results …

Euryhalinity In An Evolutionary Context, Eric T. Schultz, Stephen D. Mccormick

EEB Articles

This chapter focuses on the evolutionary importance and taxonomic distribution of euryhalinity. Euryhalinity refers to broad halotolerance and broad halohabitat distribution. Salinity exposure experiments have demonstrated that species vary tenfold in their range of tolerable salinity levels, primarily because of differences in upper limits. Halotolerance breadth varies with the species’ evolutionary history, as represented by its ordinal classification, and with the species’ halohabitat. Freshwater and seawater species tolerate brackish water; their empirically-determined fundamental haloniche is broader than their realized haloniche, as revealed by the halohabitats they occupy. With respect to halohabitat distribution, a minority of species (<10%) are euryhaline. Habitat-euryhalinity is prevalent among basal actinopterygian fishes, is largely absent from orders arising from intermediate nodes, and reappears in the most derived taxa. There is pronounced family-level variability in the tendency to be halohabitat-euryhaline, which may have arisen during a burst of diversification following the Cretaceous-Palaeogene extinction. Low prevalence notwithstanding, euryhaline species are potent sources of evolutionary diversity. Euryhalinity is regarded as a key innovation trait whose evolution enables exploitation of new adaptive zone, triggering cladogenesis. We review phylogenetically-informed studies that demonstrate freshwater species diversifying from euryhaline ancestors through processes such as landlocking. These studies indicate that some euryhaline taxa are particularly susceptible to changes in halohabitat and subsequent diversification, and some geographic regions have been hotspots for transitions to freshwater. Comparative studies on mechanisms among multiple taxa and at multiple levels of biological integration are needed to clarify evolutionary pathways to, and from, euryhalinity.

Evidence For Pit-Type (Slc20) And Napi-Ii-Type (Slc34) Transporters In The Rat Choroid Plexus, Hien M. Le

Honors Scholar Theses

: A major function of the brain choroid plexus (CP) is to regulate the exchange of solutes between the blood plasma and the cerebrospinal fluid (CSF) using selective transporters. CSF inorganic phosphate (P_i) concentration is maintained at about one-half that of plasma and is potentially important because of its regulatory, structural, and biochemical functions. Phosphate is critical for ATP and DNA formation, the linked regulation between phosphate and calcium, and as an intracellular buffer. The human body has two major P_i transporter gene families known as SLC34 (NaPi-II) and SLC20 (PiT), which have wide tissue distribution. Although …

The Effects Of Rectal Temperature And Hydration Status On Perceptual Ratings In Dehydrating Males, Ethan A. Talbot

Honors Scholar Theses

Athletes push the limits of what the human body can handle every day. When they exercise in the heat, they can attain dangerous levels of internal temperature and dehydration. Since athletes are sometimes not aware when they are experiencing severe hyperthermia or hypohydration, it is of interest to anyone who exercises in the heat to study whether athletes are consciously aware that they are approaching dangerous physiological limits. This study compares the perceptual values of athletes exercising in the heat to the changes in their internal temperature and hydration status, to see if athletes can reliably predict their heat and …

Salinity Preference Of Alaskan Threespine Stickleback: Test For Divergence In Halotaxis Between Ancestral And Landlocked Populations, David Fryxell, Eric T. Schultz

EEB Articles

Glacial retreat during the Pleistocene caused landlocking of anadromous Alaskan threespine stickleback, Gasterosteus aculeatus, furnishing a natural ‘experiment’ in osmoregulatory divergence. The objective of this study was to assess the effects of individual acclimation and population divergence on salinity preference. Full-sibling families of marine, anadromous, and freshwater-landlocked populations of stickleback were reared in common environments until 3 weeks post-hatch, then were split and acclimated to low or high salinity. At 6 to 8 weeks of age the six experimental groups were tested for salinity preference in a tank that offers fish a choice of compartments with different salinities arranged …

Changes In The Proliferation Of The Subventricular Zone Neural Stem Cell Pool Throughout Aging In The Murine Brain, Olayinka Edwards

Honors Scholar Theses

Previous studies regarding subventricular zone (SVZ) neural stem cells (NSCs) have either observed global changes in the SVZ niche containing NSCs or an impure NSC population. By imaging wholemount preparations of mouse brains and staining with molecular markers specific for proliferating NSC nuclei, the study was able to give a more accurate depiction of the SVZ NSC population than its predecessors. This study will quantify the percentage of proliferating NSCs at various ages of adult murine brain development in order to elucidate a possible correlation between NSC division kinetics and the declining neurogenic output witnessed with aging.

Investigating The Diversity Of Radial Glia Fates In The Rat Neocortex, Abraham William Aron

Honors Scholar Theses

Radial Glia (RG) are a mitotically active population of cells which reside within the ventricular zone at the lateral ventricle and give rise to the pyramidal neurons and astrocytes of the neocortex. Through cellular divisions, RG produce two daughter cells, one which resides in the ventricular zone and becomes another RG while the other is an immature progenitor which migrates away from the ventricle and populates the growing cortex. RG have been found to be a heterogeneous population of cells which express different surface antigens and genetic promoters which may influence the cellular fate of their progeny. In this study …

Oxygen Supplementing, Biocompatible Outer Membranes For Enhanced Performance Of Implantable Glucose Sensors, Hardeep Singh

Honors Scholar Theses

Lack of linearity and sensitivity, oxygen dependence, biofouling and tissue inflammation hinder the development of implantable biosensors for continuous monitoring of glucose. Herein, we report the development of stacked outer membranes based on LBL/PVA hydrogels that improve sensor sensitivity, linearity, oxygen independence and counter biofouling and inflammation. While the inner LBL membrane affords tunable diffusivity, the outer PVA is capable of releasing anti-inflammatory drugs/tissue response modifying agents to counter acute and chronic inflammation, and to induce neo-angiogenesis at the implant site. Sensors were fabricated by immobilizing GOx enzyme on top of 50 μm platinum wires, followed by deposition of stacked …

Changes In Mirna Expression In A Model Of Microcephaly, Shan Parikh

Honors Scholar Theses

miRNAs function to regulate gene expression through post-transcriptional mechanisms to potentially regulate multiple aspects of physiology and development. Whole transcriptome analysis has been conducted on the citron kinase mutant rat, a mutant that shows decreases in brain growth and development. The resulting differences in RNA between mutant and wild-type controls can be used to identify genetic pathways that may be regulated differentially in normal compared to abnormal neurogenesis. The goal of this thesis was to verify, with quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), changes in miRNA expression in Cit-k mutants and wild types. In addition to confirming miRNA expression …