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Full-Text Articles in Engineering
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 …
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 …
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 …
Acute Oxygen-Sensing By The Carotid Bodies : The Thermal Microdomain Model, Ryan Joseph Rakoczy
Acute Oxygen-Sensing By The Carotid Bodies : The Thermal Microdomain Model, Ryan Joseph Rakoczy
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The carotid bodies (CB) are peripheral chemoreceptors that detect changes in arterial oxygenation and, via afferent inputs to the brainstem, correct the pattern of breathing to restore blood gas homeostasis. Elucidating the “signal” that couples carotid body sensory type I cell (CBSC) hypoxic mitochondrial inhibition with potassium channel closure has proven to be an arduous task; to date, a multitude of oxygen-sensing chemotransduction mechanisms have been described and altercated (Varas, Wyatt & Buckler, 2007; Gao et al, 2017; Rakoczy & Wyatt, 2018). Herein, we provide preliminary evidence supporting a novel oxygen-sensing hypothesis suggesting CBSC hypoxic chemotransductive signaling may in part …
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 …
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. …
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 …
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 …
Alterations In Cardiac Motions Of The Failing Heart During Direct Mechanical Ventricular Actuation, Benjamin Allyn Schmitt
Alterations In Cardiac Motions Of The Failing Heart During Direct Mechanical Ventricular Actuation, Benjamin Allyn Schmitt
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Objectives: Heart failure (HF) refractory to medical management can be effectively treated with mechanical support. However, available devices are frequently associated with complications due to blood contact. Direct cardiac compression (DCC) devices augment LV systolic pump function by externally compressing the heart surface. Direct Mechanical Ventricular Actuation (DMVA) is a unique DCC method providing not only systolic but, importantly, diastolic support. However, DCC in general remains a relatively poorly understood modality. The purpose of this study was to examine DMVA’s effect on restoration of physiologic function in the failing heart. Methods: Global ischemic HF was induced with 5 mins of …
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 …
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 …
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. …
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. …
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 …
Renca Macrobeads Inhibit Tumor Cell Growth Via Egfr Activation And Regulation Of Mef2 Isoform Expression, Prithy Caroline Martis
Renca Macrobeads Inhibit Tumor Cell Growth Via Egfr Activation And Regulation Of Mef2 Isoform Expression, Prithy Caroline Martis
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Tumors are heterogeneous systems, whose growth is influenced by intrinsic properties of malignant cells, external systemic factors (i.e. immune, neural, endocrine, etc.), and the dynamic interactions between tumor cells and their microenvironment. Given the inherent complexity of cancers, combined with the continual evolution of tumors and the development of treatment resistance, a precision medicine approach may not provide an optimal clinical response. Exploring a new paradigm that focuses on regulating cancer as a system may not only control tumor progression but also address the extraordinary challenges of tumor heterogeneity and disease recurrence in order to improve clinical outcomes. As a …
Global Identification Of Human Modifier Genes Of Alpha-Synuclein Toxicity, Ishita Haider
Global Identification Of Human Modifier Genes Of Alpha-Synuclein Toxicity, Ishita Haider
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Alpha-synuclein is a small lipid binding protein abundantly expressed in the brain. Lewy body or Lewy-like pathology, primarily composed of misfolded alpha-synuclein, is a pathological feature shared by several neurodegenerative disorders, including Parkinson's disease (PD). Both missense mutations and increased copy numbers of the SNCA gene, encoding the alpha-synuclein protein, have been genetically linked to autosome dominant PD. Other genetic variations affecting the expression of the SNCA gene have been associated with sporadic PD. Although the physiological function of alpha-synuclein is not well understood, its localization to plasma and vesicular membranes at the presynaptic terminals suggests a role in neurotransmission. …
Ultraviolet-B Radiation Induces Release Of Bioactive Microvesicle Particles In Keratinocytes Via Platelet-Activating Factor And Acid Sphingomyelinase, Langni Liu
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Ultraviolet-B (UV-B) radiation is one of the most common environmental factors and is known to induce the production of bioactive agents that cause several diseases including skin cancer. UVB exposure stimulates the production of a phospholipid activator, platelet-activating factor (PAF), and its analogs in keratinocytes that activate the PAF receptor (PAF-R) resulting in acute inflammatory and delayed systematic immunosuppressive effects. However, as UVB only penetrates into the skin epidermal layer, the detailed mechanisms of how UVB exerts systematic effects remains unclear. Previously we found that UVB induces keratinocytes to release large numbers of microvesicle particles (MVPs). These small membrane-bound particles …
Differential Microrna Expression In Barrett's Esophagus Correlates With Regulation Of Posterior Homeotic Genes, Reilly June Clark
Differential Microrna Expression In Barrett's Esophagus Correlates With Regulation Of Posterior Homeotic Genes, Reilly June Clark
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Barrett’s Esophagus (BE) is characterized by the appearance of an intestinal-like epithelium in the distal esophagus. The molecular mechanisms behind BE development are unknown. BE is often preceded by Gastroesophageal Reflux Disease (GERD) and predisposes patients to esophageal adenocarcinoma (EAC). Due to the high mortality rate associated with EAC, BE patients are continuously monitored through upper endoscopy with biopsy for progression to low grade dysplasia (LGD), high grade dysplasia, and EAC. This monitoring technique poses numerous risks, so alternative surveillance and diagnostic techniques for BE pathogenesis are continually studied. microRNA biomarkers in BE pathogenesis may provide alternative means of diagnosis …
Mitochondria-Dependent Cellular Toxicity Of Α-Synuclein Modeled In Yeast, Rajalakshmi Santhanakrishnan
Mitochondria-Dependent Cellular Toxicity Of Α-Synuclein Modeled In Yeast, Rajalakshmi Santhanakrishnan
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Parkinson’s disease is the second most common neurodegenerative disease. This disease is caused by the degeneration of dopaminergic neurons, leading to debilitating motor symptoms and early mortality. The protein α-synuclein (α-syn), encoded by SNCA, misfolds and forms inclusions in Parkinson’s disease brains. When α-syn is overexpressed in yeast, it causes cellular toxicity and an increased number of aggregates, recapitulating the toxic phenotypes observed in humans and animal models. Yeast models are a powerful tool to perform high-throughput overexpression screening to identify modifiers of α-syn toxicity. α-syn causes mitochondrial dysfunction by inhibiting complex I and inducing mitochondrial fragmentation. Prior screening of …
Type 2 Diabetes Leads To Impairment Of Cognitive Flexibility And Disruption Of Excitable Axonal Domains In The Brain, Leonid M. Yermakov
Type 2 Diabetes Leads To Impairment Of Cognitive Flexibility And Disruption Of Excitable Axonal Domains In The Brain, Leonid M. Yermakov
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Type 2 diabetes is a metabolic disease affecting millions of people around the world. Cognitive and mood impairments are among its many debilitating complications, but disease mechanism(s) remain elusive. Here, we present a series of behavioral tasks that demonstrate impairment of cognitive flexibility in db/db mice, a commonly used type 2 diabetes model. Using immunohistochemistry, we demonstrate disruption of axon initial segments (AIS) and nodes of Ranvier, excitable axonal domains regulating neuronal output, in brain regions associated with cognitive and mood impairments. Finally, we present results of exercise treatment that ameliorates AIS disruption in these animals. Establishing cognitive flexibility deficits …
Biomarker-Performance Associations During Nutritional And Exercise Intervention In Air Force Personnel, Jennifer Jurcsisn
Biomarker-Performance Associations During Nutritional And Exercise Intervention In Air Force Personnel, Jennifer Jurcsisn
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This study evaluated the combined effects of an exercise intervention and nutritional supplement on biomarkers of stress and resilience, and the relationships of those markers with physical and cognitive performance. 130 healthy Active-Duty Air Force (AF) personnel were recruited to participate in a double-blind, placebo controlled 12-week exercise and nutritional intervention. Serum was collected at basal and high stress conditions pre- and post-intervention to track the following biomarkers: cortisol, dehydroepiandrosterone-sulfate (DHEA-S), norepinephrine (NE), neuropeptide Y (NPY), and serotonin. The exercise intervention significantly attenuated the cortisol response and peak stress cortisol levels. The nutritional intervention decreased peak stress NE. The selected …
A Novel Approach For Cancer Characterization Using Latent Dirichlet Allocation And Disease-Specific Genomic Analysis, Hima Bindu Yalamanchili
A Novel Approach For Cancer Characterization Using Latent Dirichlet Allocation And Disease-Specific Genomic Analysis, Hima Bindu Yalamanchili
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Two challenging problems in the clinical study of cancer are the characterization of cancer subtypes and the classification of individual patients according to those subtypes. Further, understanding the role of differential gene expression in the development of and molecular response to cancer is a complex problem that remains challenging, in part due to the sheer number of genes and gene products involved. Traditional statistical approaches addressing these problems are hindered by within-class heterogeneity and challenges inherent in data integration across high-dimensional data. In addition, many current machine learning methods do not lend themselves to biological interpretation. We have developed a …
Context-Dependence Of Physiological Systems: Environment-Physiology Interactions In The Respiratory Control System, Joseph M. Santin
Context-Dependence Of Physiological Systems: Environment-Physiology Interactions In The Respiratory Control System, Joseph M. Santin
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We know that animals are tuned to survive different environmental conditions or else life would not exist. Unfortunately, this is often forgotten or ignored when designing experiments. As Marsh Tenney articulated, "The physiologist keeps the whole always in mind. He accepts the tactical necessity of reductionism to understand parts, but, once done, for him it is only the beginning, never the end” (from Remmers, 2005). In an era when it is all too common to take environmental complexity out of the organism to understand physiology, my work puts some of that complexity back in the study of organisms. I take …
Functions Of The Apical Na+/ K+/ 2cl- Cotransporter 1 In Choroid Plexus Epithelial Cells., Jeannine Marie Crum Gregoriades
Functions Of The Apical Na+/ K+/ 2cl- Cotransporter 1 In Choroid Plexus Epithelial Cells., Jeannine Marie Crum Gregoriades
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Choroid plexus epithelial cells (CPECs) secrete cerebrospinal fluid (CSF) and regulate its electrolyte composition. CPECs express both the Na+/ K+ ATPase and the Na+/ K+/ 2Cl- cotransporter 1 (NKCC1) on their apical membrane (CSF facing), deviating from the typical basolateral membrane location in chloride secretory epithelia. Given this unusual location of NKCC1 and the unknown intracellular Na+ and Cl- concentrations of CPECs, the cotransporter function in these cells is not understood. Further, the direction of net ion and associated water fluxes mediated by NKCC1 under basal physiological conditions in CPECs …
Persistent Inward Currents Play A Role In Muscle Dysfunction Seen In Myotonia Congenita, Ahmed Alaa Hawash
Persistent Inward Currents Play A Role In Muscle Dysfunction Seen In Myotonia Congenita, Ahmed Alaa Hawash
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Myotonia congenita is a rare skeletal muscle channelopathy caused by a reduced chloride channel (ClC-1) current, which results in debilitating muscle hyperexcitability, prolonged contractions, and transient episodes of weakness. The excitatory events that trigger myotonic action potentials in the absence of stabilizing ClC-1 current are not fully understood. My in vitro intracellular recordings from a mouse homozygous knockout of ClC-1 revealed a slow after-depolarization (AfD) that triggers myotonic action potentials. The AfD is well-explained by a tetrododoxin-sensitive and voltage-dependent Na+ persistent inward current (NaPIC). Notably, this NaPIC undergoes slow inactivation over seconds, thus providing the first mechanistic explanation for the …
Novel Mechanisms Underlying Warm-Up And Percussion Myotonia In Myotonia Congenita, Kevin Richard Nnovak
Novel Mechanisms Underlying Warm-Up And Percussion Myotonia In Myotonia Congenita, Kevin Richard Nnovak
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Patients with myotonia congenita have muscle hyperexcitability due to loss-of-function mutations in the ClC-1 chloride channel in skeletal muscle, which causes spontaneous firing of muscle action potentials (myotonia), producing muscle stiffness. Triggers for myotonia can occur voluntarily at the neuromuscular junction or involuntarily by striking the muscle with a reflex hammer (percussion myotonia). In patients, muscle stiffness lessens with exercise, a change known as the warm-up phenomenon. Our goal was to identify the mechanism underlying warm-up and percussion myotonia and to use this information to guide development of novel therapies. To determine these underlying mechanisms, we used a drug to …
Sensorimotor Deficits Following Oxaliplatin Chemotherapy, Jacob Adam Vincent
Sensorimotor Deficits Following Oxaliplatin Chemotherapy, Jacob Adam Vincent
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Neurotoxicity is one of the most significant side effects diminishing clinical efficacy and patient quality of life during and following chemotherapy. Oxaliplatin (OX) is a platinum based chemotherapy agent used in the treatment of colorectal cancer. Colorectal cancer currently ranks as the 4th most common cancer, and the majority of patients receive OX as a part of their adjuvant therapy. OX based adjuvant therapies significantly improve 5 year survival rates, however in many cases patients must stop treatment early because of the neurotoxic side effects. OX causes two clinically distinct forms of neurotoxicity. Acutely, within hours and for days following …
Identification Of Novel Ligands And Structural Requirements For Heterodimerization Of The Liver X Receptor Alpha, Shimpi Bedi
Identification Of Novel Ligands And Structural Requirements For Heterodimerization Of The Liver X Receptor Alpha, Shimpi Bedi
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LXRs, LXRa (NR1H3) and LXRß (NR1H2), are ligand-activated transcription factors that are members of the nuclear receptor superfamily. Oxysterols and nonsteroidal synthetic compounds bind directly to LXRs and influence the expression of LXR dependent genes. The use of murine models and LXR-selective agonists have established the important role of LXRs as sterol sensors that govern the absorption, transport, and catabolism of cholesterol. Upon activation, these receptors have been shown to increase reverse cholesterol transport from the macrophage back to the liver to aid in the removal of excess cholesterol. Not surprisingly, LXR dysregulation is a feature of several human diseases, …
Analytical-Based Methodologies To Examine In Vitro Nanokinetics Of Silver Nanoparticles, Sesha Lakshmi Arathi Paluri
Analytical-Based Methodologies To Examine In Vitro Nanokinetics Of Silver Nanoparticles, Sesha Lakshmi Arathi Paluri
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Advancements in the nanotechnology have taken a huge leap in 21st century resulting in 1814 consumer products containing nanomaterials. About 47% of these products belong to the health and fitness sector and ~24% utilize silver nanoparticles (AgNPs). Despite the promising biomedical applications of AgNPs (e.g. bone cements, contrasting agents, and drug-carriers), lack of standardized methods for examining their nanokinetics (i.e., Absorption, Distribution, Metabolism, and Elimination (ADMEs)) limit their clinical implementation. The current work addresses this knowledge gap by developing analytical-based approaches for studying in vitro ADMEs of AgNPs. To demonstrate the versatility of these methodologies, two in vitro kidney study …
Dysregulation Of Phospholipase D (Pld) Isoforms Increases Breast Cancer Cell Invasion, Kristen Fite
Dysregulation Of Phospholipase D (Pld) Isoforms Increases Breast Cancer Cell Invasion, Kristen Fite
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Breast cancer remains the second most prevalent cancer among women in the U.S. with metastatic breast cancer having the worst prognosis. A rapidly proliferating tumor under various stressors will promote phenotypic cellular changes, known as epithelial-to-mesenchymal transition (EMT), which allows cells to begin to invade surrounding tissue, enter the circulatory system, and eventually seed a distant metastatic site. The phospholipase D (PLD) enzymes are critical regulators of cell signaling pathways necessary for cell migration. While the importance of PLD enzymes in cancer cell invasion is well known, clinically applicable methods of PLD inhibition are not yet available. The best-studied isoforms …