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Enhanced Diagnostics And Surveillance Of Enteroviruses Including Serotypes Associated With Acute Flaccid Myelitis, Denise Lynette Kramer
Enhanced Diagnostics And Surveillance Of Enteroviruses Including Serotypes Associated With Acute Flaccid Myelitis, Denise Lynette Kramer
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Prior to 2014, Enterovirus D68 infections typically caused symptoms resembling the common cold. From 2014-2018, D68 was associated with an increase in acute flaccid myelitis. However, since 2020, neurological complications have all but disappeared. We selected 1076 respiratory specimens previously determined to be positive for rhinovirus or enterovirus from Department of Defense members and their beneficiaries collected globally from October 2018 through January 2024 and underwent sequencing. Of these specimens, 93.7% were identified as rhinoviruses, while 6.3% were enteroviruses, including 30 enterovirus D68. We utilized the Nextstrain bioinformatic pipeline to reconstruct the phylogenetic relationship of these 30 D68 viruses. Twenty-two …
Vagus Nerve Stimulation Ameliorates Cognitive Impairment Caused By Hypoxia, Birendra Sharma
Vagus Nerve Stimulation Ameliorates Cognitive Impairment Caused By Hypoxia, Birendra Sharma
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Hypoxia disrupts brain function due to the high demand for oxygen, leading to significant cognitive impairments. While vagus nerve stimulation (VNS) has been shown to enhance cognition, its ability to counteract hypoxia-induced deficits remains unclear. In this study, male Sprague–Dawley rats were assigned to sham, hypoxia, or VNS + hypoxia groups, with VNS delivered during hypoxia (8% oxygen) using biphasic pulses (100 μs, 30 Hz, 0.8 mA). Cognitive performance was evaluated using multiple behavioral paradigms, and hippocampal tissue was analyzed for neurotrophin expression through quantitative PCR and immunohistochemistry. Among the behavioral measures, hypoxia specifically impaired performance on the passive avoidance …
The Role Of Trpm7 In Mouse Development And Immune Cell Function, Jananie Rockwood
The Role Of Trpm7 In Mouse Development And Immune Cell Function, Jananie Rockwood
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Transient receptor melastatin 7 (TRPM7) functions both as an ion channel and a protein kinase. TRPM7 has been implicated in Mg2+ homeostasis, embryogenesis, cardiac automaticity, and immunity. The purpose of this research was to deepen our understanding of TRPM7 channel and kinase functions. To this end, we used two transgenic mouse models: the TRPM7 gain-of-function (GOF) and TRPM7 kinase-dead (KD) mice to address the consequences of increased channel activity and kinase inactivation, respectively. Global deletion of TRPM7 or the kinase domain alone are embryonic lethal, therefore, we used the TRPM7 GOF mouse to investigate germline transmission. We examined embryo development …
Induced Reduction Of N-Glycosylation Leads To Heart Failure, Anthony M. Young
Induced Reduction Of N-Glycosylation Leads To Heart Failure, Anthony M. Young
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Cardiovascular disease is the leading cause of death and contributes to the increasing global prevalence of heart failure (HF). N-glycosylation is a common co-/post-translational modification where branching oligosaccharides are bound to the extracellular domain of membrane proteins. This creates a diverse range of glycan structures and requires the coordination of hundreds of regulated genes. Inherited mutations in glycan synthesis frequently present with cardiomyopathies leading to HF with reduced ejection fraction (HFrEF). Additionally, gene expression studies of HFrEF patients have shown altered expression of glycosylation-related genes, including alpha-1,3-mannosyl-glycoproten 2-beta-N acetlyglucosaminyltransferase (Mgat1). This gene encodes N-acetylglucosaminyl transferase 1 (GlcNAcT1) which is required …
The Impact Of Ahr And Hs1.2 Enhancer Genetic Variations On Igh Expression And Antibody Production In Human B Cells, Mili Santosh Bhakta-Yadav
The Impact Of Ahr And Hs1.2 Enhancer Genetic Variations On Igh Expression And Antibody Production In Human B Cells, Mili Santosh Bhakta-Yadav
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Antibody production is an essential component of the immune response against pathogens. The immunoglobulin heavy chain (IgH) gene codes for the heavy chain of antibodies. The IgH constant regions Cμ, Cδ, Cγ1-4, Cα1-2, and Cε encode the five major classes of antibodies, i.e., IgM, IgD, IgG1-4, IgA1-2, and IgE, respectively. The transcription of the IgH gene and class switch from IgM to other isotypes is regulated by two 3’ IgH regulatory regions (3’IgHRRs), each of which is a cluster of three enhancer regions (hs3, hs1.2 and hs4). The genetic variations in the hs1.2 enhancer have been identified; a ~53 bp …
Evaluation And Modulation Of The Circadian Clock In Human Keratinocytes And Epidermal Skin, William Harold Cvammen Iv
Evaluation And Modulation Of The Circadian Clock In Human Keratinocytes And Epidermal Skin, William Harold Cvammen Iv
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The circadian clock is a fundamental biological mechanism that regulates various physiological processes, including DNA repair, to synchronize with the day-night cycle. In human skin, exposure to ultraviolet (UV) light poses a significant challenge, inducing DNA damage that must be efficiently repaired to maintain genomic integrity and prevent carcinogenesis. This study delved into the complex interplay between the circadian clock, UV light exposure, DNA repair, and modulation of circadian transcriptional machinery in human skin. Initially, we examined the transcriptomic profile of the circadian clock in humans through in silico-based approaches and in vivo studies, revealing that core clock gene expression …
Potential Role Of Ttt Complex In Regulating Dna Replication Checkpoint In The Fission Yeast Schizosaccharomyces Pombe, Sankhadip Bhadra
Potential Role Of Ttt Complex In Regulating Dna Replication Checkpoint In The Fission Yeast Schizosaccharomyces Pombe, Sankhadip Bhadra
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DNA replication can be perturbed by various agents that slow or stall the replication forks, causing replication stress. If undetected, stressed forks may collapse, causing mutagenic DNA damage or cell death. In response to replication stress and DNA damage, the eukaryotic cell activates the DNA replication checkpoint (DRC) and DNA damage checkpoint (DDC) pathways to promote DNA synthesis, repair, and cell survival. The two cell cycle checkpoint pathways are controlled by the protein sensor kinases Rad3 (hATR/scMec1) and Tel1 (hATM/scTel1) in fission yeast, although Tel1 plays a minimal role in checkpoint functions. Rad3 and Tel1 belong to a family of …
Novel Approaches To Treatment Of Hyperexcitability In Skeletal Muscle, Phillip Vance Walker Ii
Novel Approaches To Treatment Of Hyperexcitability In Skeletal Muscle, Phillip Vance Walker Ii
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Myotonia Congenita (MC) is a rare, inherited ion channelopathy caused by a loss-of-function mutation in the CLCN1 gene. The resulting downregulation of the skeletal muscle chloride channel (ClC-1) results in hyperexcitable skeletal muscle fibers that fire action potentials involuntarily. Patients with MC suffer from debilitating stiffness due to myotonia, described clinically as delayed muscle relaxation following voluntary contraction. Skeletal muscle is a unique system we use in this study to advance our understanding of the pathophysiology underlying MC, and other channelopathies characterized by hyperexcitable cells (i.e., forms of epilepsy and cardiac arrhythmia). Furthermore, re-assessing what makes anti-myotonic drugs such as …
A Novel In-Vitro Approach To Investigate The Molecular Interaction Between Inhaled Particles And The Human Pulmonary Surfactant System, Bryan Mayville
A Novel In-Vitro Approach To Investigate The Molecular Interaction Between Inhaled Particles And The Human Pulmonary Surfactant System, Bryan Mayville
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The deployment of military personnel to austere environments poses significant pulmonary health risks from inhalation of particulates including sand, dust, pollution, and heavy machinery exhaust. When particles are less than 10 µm in diameter, they can penetrate deep within the alveoli and embed within the protective lung surfactant monolayer. Here, absorption of surfactant lipids to the particle surface disrupts the essential monolayer configuration needed to reduce surface tension and prevent atelectasis, thus leading to disease. Currently, there are no in vitro surfactant-producing lung cell models capable of studying the effects of inhaled particles on the human pulmonary surfactant system. A549 …
Insights Into Hyperkalemic Periodic Paralysis: Novel Mechanisms And Treatments, Christopher Dupont
Insights Into Hyperkalemic Periodic Paralysis: Novel Mechanisms And Treatments, Christopher Dupont
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Hyperkalemic Periodic Paralysis (hyperKPP) is an inherited channelopathy that leads to incapacitating episodes marked by severe skeletal muscle weakness or total paralysis, often accompanied by muscular stiffness (myotonia). The periods of muscle dysfunction are thought to be caused by the elevation in extracellular potassium (K). This autosomal dominant disorder is associated with mutations in the skeletal muscle voltage-gated sodium channel (Nav1.4). A multitude of inciting factors have been documented, including rest post-exertion, a potassium-rich diet, exposure to cold temperatures, psychological stressors, and fatigue. Given the variability of the triggers and the debilitating manifestation of symptoms, individuals afflicted by hyperKPP have …
Friend Or Foe? The Role Of Transforming Growth Factor-Β (Tgfβ) Signaling In Calcineurin Inhibitor-Induced Renal Damage, Adaku Uwe
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With its incorporation into clinical practice in the early 1980s, the class of pharmacological agents known as calcineurin inhibitors (CNIs) quickly became the cornerstone of immunosuppressive therapy post-organ transplantation. However, its use is limited by irreversible kidney damage in the form of renal fibrosis. The molecular mechanism by which CNIs induce renal fibrosis remains to be better understood, and to date, there are no specific therapeutic strategies to mitigate this damage. This dilemma presents a critical need to explain mechanisms by which CNIs cause renal damage. Kidneys of patients on chronic CNI therapy show increased expression of the proinflammatory cytokine …
Lipin1 Overexpression Ameliorates The Dystrophic Phenotype In Mdx Mice By Enhancing Myofiber Membrane Integrity, Abdullah Alshudukhi
Lipin1 Overexpression Ameliorates The Dystrophic Phenotype In Mdx Mice By Enhancing Myofiber Membrane Integrity, Abdullah Alshudukhi
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Duchenne muscular dystrophy (DMD) is a severe disease characterized by a progressive muscle fiber loss. DMD affects approximately 1 in 3500 male births worldwide. Patients die at early ages due to failure of respiratory and cardiac functions. DMD is caused by mutations in dystrophin gene. Loss of dystrophin leads to disruption of the membrane integrity and necroptosis in skeletal muscles of DMD patients contributing to muscle fiber loss. Currently, effective therapies for DMD have not been established. The goal of this project is to find mechanisms that may improve muscle function/structure despite dystrophin deficiency. Our data show that the expression …
Unfolding The Link Between The Axon Initial Segment, Endoplasmic Reticulum Stress, And Cognitive Impairment In Type 2 Diabetes, Jennae Shelby
Unfolding The Link Between The Axon Initial Segment, Endoplasmic Reticulum Stress, And Cognitive Impairment In Type 2 Diabetes, Jennae Shelby
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Dementia and mild cognitive impairment are well recognized comorbidities of type 2 diabetes, termed diabetic encephalopathy, that lack in course modifying treatment options. The axon initial segment (AIS) is a critical mediator of neuronal output. Shortening of AIS length has been shown to decrease neuronal excitability and is implicated in diabetic encephalopathy. AIS shortening may be reversible, hence investigating the mechanism responsible could address this significant gap in patient care by providing new therapeutic targets. Endoplasmic reticulum (ER) stress, a cellular condition that activates the unfolded protein response has been implicated in diabetic encephalopathy. Here, using immunocytochemistry in primary mouse …
Identifying A Novel Ferrocene Derivative As A K-Ras Inhibitor, Kristen Marie Rehl
Identifying A Novel Ferrocene Derivative As A K-Ras Inhibitor, Kristen Marie Rehl
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Ras proteins are small GTPases that regulate cell proliferation, differentiation and survival at the plasma membrane (PM). There are three Ras isoforms ubiquitously expressed in mammalian cells: H-, N- and K-Ras. Constitutively active Ras mutations are found in ~19% of all human cancers, with ~75% of those being in K-Ras. There are K-Ras inhibitors in clinic but they only target the oncogenic K-RasG12C mutant, which only makes up a small sub-set of K-Ras-driven cancers. Thus, there still exists a need for a pan anti-K-Ras drug. Ferrocene derivatives are a class of compounds that have been shown to inhibit the growth …
Calpains In The Peripheral Nerve And During Demyelination And Degeneration In Rodents, John A. Miller
Calpains In The Peripheral Nerve And During Demyelination And Degeneration In Rodents, John A. Miller
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Myelin formed around axons ensures rapid and efficient action potential propagation. Disruption of myelinated axons in the peripheral nervous system (PNS) often causes nerve conduction failure, neurological symptoms and can lead to long-term disability. Calpains are calcium dependent cysteine proteases that play many roles during both normal physiology and pathogenesis. Calpain-1 (CAPN1) and calpain-2 (CAPN2) are key calpain paralogs found in the nervous system and potentially have opposing roles, with CAPN2 having a more neurodegenerative function. In the central nervous system (CNS), calpains have a role in developmental myelination as well as in the pathological demyelination of multiple sclerosis and …
Lipin1 Improves Membrane Integrity In Dystrophic Muscles Of Mdx Mice, Abdulrahman Jama
Lipin1 Improves Membrane Integrity In Dystrophic Muscles Of Mdx Mice, Abdulrahman Jama
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Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder that affects 1 in 3500 male births worldwide. It is characterized by mutations in the dystrophin gene that results in the loss of functional dystrophin. Dystrophin deficiency leads to instability of the sarcolemma alongside increased inflammation, necrosis and fibrosis resulting in membrane rupture and eventual muscle fiber death. There are currently no effective treatments for DMD. Here we show that Lipin1 expression is significantly downregulated at the mRNA and protein levels in gastrocnemius muscle of mdx mice, the DMD mouse model. Lipin1 has a dual function as a phosphatidic acid phosphatase …
Dna Instability At (Attct) Microsatellites In Human Cells, Venicia Alhawach
Dna Instability At (Attct) Microsatellites In Human Cells, Venicia Alhawach
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Microsatellites are short tandem repeats of DNA (1-9 nucleotides) that are unstable in the genome. They can expand and contract which leads to mutations and rearrangements that jeopardize genomic integrity. When encountered by a replication fork, repeats of these microsatellites can form non-B DNA structures which cause replication forks to stall and collapse eventually leading to double stranded breaks (DSBs) and replication stress. One form of repair of replication dependent DSBs happens via break induced replication (BIR), a highly mutagenic repair pathway. The main objective of this study is to understand how ATTCT pentanucleotide repeats affect replication and chromosomal instability …
Microsatellite Induced Genomic Instability And Mutagenesis Through Break Induced Replication, Rujuta Yashodhan Gadgil
Microsatellite Induced Genomic Instability And Mutagenesis Through Break Induced Replication, Rujuta Yashodhan Gadgil
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Faithful DNA replication is essential to maintain genomic integrity. Compromises in this process are among the prime causes of cancer and other genetic disorders. Among several factors that can interfere with error-free DNA replication, the formation of non-B DNA structures by microsatellite sequences is critical. Microsatellites are 1-9 bp long tandem repetitive regions that can form secondary structures like hairpins, triplex, Gquadruplex etc. and undergo expansions due to replication fork stalling to cause several diseases. Hairpin forming microsatellites have been shown to induce DNA DSBs and lead to genetic instability and mutagenesis. The goal of this study is to understand …
Fbxl16 Promotes Breast Cancer Cell Growth And Diminishes Fulvestrant Responsiveness By Stabilizing Erα Protein, Krushangi Nirav Shah
Fbxl16 Promotes Breast Cancer Cell Growth And Diminishes Fulvestrant Responsiveness By Stabilizing Erα Protein, Krushangi Nirav Shah
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Breast cancer is the most prevalent cancer in women. Approximately 75% of breast cancers are estrogen receptor alpha positive (ER+) and are treatable with endocrine therapies and/or CDK inhibitors. However, endocrine therapy (ET) resistance and metastasis are major obstacles in advanced ERα+ breast cancer (ER+ BCa) therapeutics. Upregulated oncogenic ERα activity plays critical role in progression of ER+ BCa. One essential mechanism of regulating ERα signaling is the ubiquitination-dependent proteasomal degradation of ERα. Owing to its direct effect on ERα degradation, fulvestrant is a first-line FDA-approved ET for metastatic and locally advanced breast cancer and a second-line drug for treatment …
Reciprocal Regulation Of Transketolase-Like 1 And Hypoxia-Inducible Factor 1 Alpha In Metabolic Reprogramming And Growth Of Diffuse Midline Glioma, H3 K27m-Mutant, Christopher Andrew Waker
Reciprocal Regulation Of Transketolase-Like 1 And Hypoxia-Inducible Factor 1 Alpha In Metabolic Reprogramming And Growth Of Diffuse Midline Glioma, H3 K27m-Mutant, Christopher Andrew Waker
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Diffuse midline glioma, K27M-mutant (DMG) are intractable brain tumors, primarily occurring in the pediatric and adolescent population. Patients have a median survival of less than one year after diagnosis. A lack of therapeutic targets has been a barrier to improvement in patient survival. Irradiation therapy improves symptoms while chemotherapy and surgical intervention, for the most part, have not yet demonstrated utility for treatment. DMG are characterized by a histone H3 mutation that results in the genome-wide loss of epigenetic-repressive marks on K27 and is associated with the misexpression of genes, like Cancer/Testis antigens. A member of this group, transketolase-like 1 …
Erk3 And Dgkζ Interact To Modulate Cell Motility In Lung Cancer Cells, Amanda Myers
Erk3 And Dgkζ Interact To Modulate Cell Motility In Lung Cancer Cells, Amanda Myers
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Extracellular-regulated kinase 3 (ERK3) is overexpressed in a variety of cancers, including lung cancer. This atypical mitogen-activated protein kinase (MAPK) has a unique structure which includes a C34 domain and C-terminus and about which relatively little is known. ERK3 has been demonstrated to promote cell migration and metastasis in multiple cancer types. A yeast two-hybrid assay using ERK3 as bait indicated Diacylglycerol kinase ζ (DGKζ) is a binding partner. DGKζ is an isoform in the DGK family, all the members of which phosphorylate the lipid diacylglycerol (DAG) to generate phosphatidic acid (PA). DGKζ was shown to promote migration in mouse …
The Role Of Son In Chromatin-Mediated Gene Expression, Melissa Jordan Ward
The Role Of Son In Chromatin-Mediated Gene Expression, Melissa Jordan Ward
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Gene expression in mammalian cells requires complex nuclear choreography, and there is increasing evidence that spatiotemporal organization of chromatin and nuclear compartments plays an important role in gene expression. In this dissertation, I examined the function of SON, a splicing factor with a known role in nuclear organization, in chromatin-mediated gene expression. SON association with a transcriptionally inactive U2OS 2-6-3 reporter gene array provided a useful model to study SON’s chromatin dynamics. I demonstrated that SON associates with the inactive but not the activated array, and that SON’s RNA binding domains are not necessary for that association. Second, I discovered …
Nmr Metabolomics For Optimizing Cell-Free Protein Synthesis, Angela M. Campo
Nmr Metabolomics For Optimizing Cell-Free Protein Synthesis, Angela M. Campo
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Cell-Free Protein Synthesis (CFPS) has been utilized by biochemists to produce a variety of chemicals and therapeutics. While CFPS has spawned research in the biochemistry and medical communities, there are still unknown issues with interlaboratory variability with the technique. This work explored the black box nature of CFPS reactions by analyzing the CFPS reactions in situ with Nuclear Magnetic Resonance (NMR) spectroscopy. Aim 1 developed the protocol for conducting NMR experiments on E. coli cell-free reactions as well as a data analysis pipeline. This was accomplished with 1H NMR, capturing metabolite changes over time. The 1D NOESY experiment proved to …
Altered Skeletal Muscle Excitation-Contraction Coupling In The R6/2 Transgenic Mouse Model For Huntington's Disease, Daniel R. Miranda
Altered Skeletal Muscle Excitation-Contraction Coupling In The R6/2 Transgenic Mouse Model For Huntington's Disease, Daniel R. Miranda
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Huntington’s disease (HD) has classically been categorized as a neurodegenerative disorder. However, the expression of the disease-causing mutated huntingtin gene in skeletal muscle may contribute to the symptoms of HD, namely those that involve involuntary muscle contraction. In the R6/2 transgenic mouse model of HD, we previously observed ion channel defects that could contribute to involuntary muscle contraction. Here, in R6/2 muscle we investigated the consequence of these ion channel defects on action potentials (APs), the first step in excitation-contraction (EC) coupling. We found that the ion channel defects were associated with depolarizing the baseline membrane potential during AP trains. …
Als-Induced Excitability Changes In Individual Motorneurons And The Spinal Motorneuron Network In Sod1-G93a Mice At Symptom Onset, Christiana S.I. Draper
Als-Induced Excitability Changes In Individual Motorneurons And The Spinal Motorneuron Network In Sod1-G93a Mice At Symptom Onset, Christiana S.I. Draper
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Amyotrophic lateral sclerosis (ALS) is the most common motorneuron (MN) disease in adulthood. ALS is hallmarked by the progressive loss of MNs in the brain, brainstem, and spinal cord. Many hypotheses to explain the pathogenesis of ALS have been explored, but the exact mechanisms underlying the development of this disease remain unknown. However, abnormalities in MN excitability and glutamate excitotoxicity are the most widely studied. For decades, researchers have examined MN excitability in ALS, but the current literature is inconsistent, showing evidence of hyperexcitability, hypoexcitability, or no change in excitability of MNs in ALS. Many of these studies also focus …
Multi-Label Classification On Locally-Linear Data: Application To Chemical Toxicity Prediction, Xiu Huan Yap
Multi-Label Classification On Locally-Linear Data: Application To Chemical Toxicity Prediction, Xiu Huan Yap
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Computational models may assist in identification and prioritization of large chemical libraries. Recent experimental and data curation efforts, such as from the Tox21 consortium, have contributed towards toxicological datasets of increasing numbers of chemicals and toxicity endpoints, creating a golden opportunity for the exploration of multi-label learning and deep learning approaches in this thesis. Multi-label classification (MLC) methods may improve model predictivity by accounting for label dependence. However, current measures of label dependence, such as correlation coefficient, are inappropriate for datasets with extreme class imbalance, often seen in toxicological datasets. In this thesis, we propose a novel label dependence measure …
Carbon Nanotube-Coated Scaffolds For Tissue Engineering Applications, Soham Dipakbhai Parikh
Carbon Nanotube-Coated Scaffolds For Tissue Engineering Applications, Soham Dipakbhai Parikh
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Carbon Nanotubes (CNTs) have beneficial properties for cell scaffolding, which has translated into effective growth of bone, muscle, and cardiac cells. However, loose carbon nanotubes can cause in vivo toxicity. To reduce this risk, our team has developed biomimetic scaffolds with multiscale hierarchy where carpet-like CNT arrays are covalently bonded to larger biocompatible substrates. In this study, we have tested such scaffolds in two distinct types of biomedical applications involving glioblastoma and keratinocyte cells. The growth of glioblastoma (GBM) cells on our CNT-coated biomimetic scaffolds was evaluated to check their suitability as a potential chemotherapy-loaded implant for GBM patient treatment. …
Augmenting Structure/Function Relationship Analysis With Deep Learning For The Classification Of Psychoactive Drug Activity At Class A G Protein-Coupled Receptors, Hannah Willow Shows
Augmenting Structure/Function Relationship Analysis With Deep Learning For The Classification Of Psychoactive Drug Activity At Class A G Protein-Coupled Receptors, Hannah Willow Shows
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G protein-coupled receptors (GPCRs) initiate intracellular signaling pathways via interaction with external stimuli. [1-5] Despite sharing similar structure and cellular mechanism, GPCRs participate in a uniquely broad range of physiological functions. [6] Due to the size and functional diversity of the GPCR family, these receptors are a major focus for pharmacological applications. [1,7] Current state-of-the-art pharmacology and toxicology research strategies rely on computational methods to efficiently design highly selective, low toxicity compounds. [9], [10] GPCR-targeting therapeutics are associated with low selectivity resulting in increased risk of adverse effects and toxicity. Psychoactive drugs that are active at Class A GPCRs used …
The Regulation Of Small Gtpase Rac1 Phosphorylation, Activation And Subcellular Localization By Δnp63Α, Amjad Ahmed Aljagthmi
The Regulation Of Small Gtpase Rac1 Phosphorylation, Activation And Subcellular Localization By Δnp63Α, Amjad Ahmed Aljagthmi
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ΔNp63α, a member of the p53 family of transcription factors, plays a critical role in normal development and human disease. Loss of ΔNp63α expression is associated with increased cancer invasiveness and metastasis. The small GTPase Rac1 is a master regulator of cell motility, and increased Rac1 activity upregulates cell invasion in multiple human cancers. Increased cancer cell invasion associated with ΔNp63α knockdown and Rac1 activation suggests a novel mechanism by which ΔNp63α regulates tumor invasiveness through Rac1. Accordingly, we sought to delineate the effects of ΔNp63α on Rac1 phosphorylation, activation and subcellular localization. We identified a novel ΔNp63α/miR-320a/PKCᵧ signaling pathway …
Modeling Of Excitation In Skeletal Muscle, Sabrina Kinzie Metzger
Modeling Of Excitation In Skeletal Muscle, Sabrina Kinzie Metzger
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Recent experimental findings in the Rich lab suggest there are important gaps in our understanding of muscle excitability in various disease states. To generate and test hypotheses as well as to determine whether our current understanding of various aspects of muscle excitation can fully explain experimental findings, an accurate model of muscle excitation was needed. Previous studies have modeled excitation of muscle, but in each case, important aspects were omitted. One reason for this is that little effort has been made to accurately simulate muscle action potentials. In this thesis I present progress made towards generation of a model of …