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Role Of Ankle Peak Systolic Velocity In Predicting Healing Of Diabetic Foot Lesions In Patients With Critical Lower Limb Ischemia, Assem M. Herzallah Aug 2018

Role Of Ankle Peak Systolic Velocity In Predicting Healing Of Diabetic Foot Lesions In Patients With Critical Lower Limb Ischemia, Assem M. Herzallah

Journal of Medicine in Scientific Research

Aim We designed the study for determining if ankle peak systolic velocity (APSV) has value in prediction of healing in diabetic foot lesions in patients with critical lower limb ischemia. APSV is the mean of the peak systolic velocities estimated at the ankle level over the distal tibial arteries. Patient and Methods Patients were included if they had diabetes foot lesions. Such lesions were ulcers, gangrene, or tissue necrosis. In addition, they had nonpalpable pedal pulses. Endpoints were healed or healing foot lesions, revascularization, major amputation, or death. Fifty diabetic limbs were included. Results Twenty-five (50%) limbs with diabetic foot …


Rgs10 Shapes The Hemostatic Response To Injury Through Its Differential Effects On Intracellular Signaling By Platelet Agonists., Peisong Ma, Shuchi Gupta, Sara Sampietro, Daniel Dehelian, Valerie Tutwiler, Alan Tang, Timothy J. Stalker, Lawrence F. Brass Aug 2018

Rgs10 Shapes The Hemostatic Response To Injury Through Its Differential Effects On Intracellular Signaling By Platelet Agonists., Peisong Ma, Shuchi Gupta, Sara Sampietro, Daniel Dehelian, Valerie Tutwiler, Alan Tang, Timothy J. Stalker, Lawrence F. Brass

Department of Medicine Faculty Papers

Platelets express ≥2 members of the regulators of G protein signaling (RGS) family. Here, we have focused on the most abundant, RGS10, examining its impact on the hemostatic response in vivo and the mechanisms involved. We have previously shown that the hemostatic thrombi formed in response to penetrating injuries consist of a core of fully activated densely packed platelets overlaid by a shell of less-activated platelets responding to adenosine 5'-diphosphate (ADP) and thromboxane A2 (TxA2). Hemostatic thrombi formed in RGS10-/- mice were larger than in controls, with the increase due to expansion of the shell but not the core. Clot …


Week Of August 27, 2018, New York Medical College Aug 2018

Chronically Implanted Intracranial Electrodes: Tissue Reaction And Electrical Changes., Andrew Campbell, Chengyuan Wu Aug 2018

Chronically Implanted Intracranial Electrodes: Tissue Reaction And Electrical Changes., Andrew Campbell, Chengyuan Wu

Department of Neurosurgery Faculty Papers

The brain-electrode interface is arguably one of the most important areas of study in neuroscience today. A stronger foundation in this topic will allow us to probe the architecture of the brain in unprecedented functional detail and augment our ability to intervene in disease states. Over many years, significant progress has been made in this field, but some obstacles have remained elusive-notably preventing glial encapsulation and electrode degradation. In this review, we discuss the tissue response to electrode implantation on acute and chronic timescales, the electrical changes that occur in electrode systems over time, and strategies that are being investigated …


Map7 Regulates Axon Morphogenesis By Recruiting Kinesin-1 To Microtubules And Modulating Organelle Transport., Stephen R. Tymanskyj, Benjamin Yang, Kristen J. Verhey, Le Ma Aug 2018

Map7 Regulates Axon Morphogenesis By Recruiting Kinesin-1 To Microtubules And Modulating Organelle Transport., Stephen R. Tymanskyj, Benjamin Yang, Kristen J. Verhey, Le Ma

Department of Neuroscience Faculty Papers

Neuronal cell morphogenesis depends on proper regulation of microtubule-based transport, but the underlying mechanisms are not well understood. Here, we report our study of MAP7, a unique microtubule-associated protein that interacts with both microtubules and the motor protein kinesin-1. Structure-function analysis in rat embryonic sensory neurons shows that the kinesin-1 interacting domain in MAP7 is required for axon and branch growth but not for branch formation. Also, two unique microtubule binding sites are found in MAP7 that have distinct dissociation kinetics and are both required for branch formation. Furthermore, MAP7 recruits kinesin-1 dynamically to microtubules, leading to alterations in organelle …


N-Terminal Domain Of Human Uracil Dna Glycosylase (Hung2) Promotes Targeting To Uracil Sites Adjacent To Ssdna-Dsdna Junctions, Brian P Weiser, Gaddiel Rodriguez, Philip A Cole, James T Stivers Aug 2018

N-Terminal Domain Of Human Uracil Dna Glycosylase (Hung2) Promotes Targeting To Uracil Sites Adjacent To Ssdna-Dsdna Junctions, Brian P Weiser, Gaddiel Rodriguez, Philip A Cole, James T Stivers

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The N-terminal domain (NTD) of nuclear human uracil DNA glycosylase (hUNG2) assists in targeting hUNG2 to replication forks through specific interactions with replication protein A (RPA). Here, we explored hUNG2 activity in the presence and absence of RPA using substrates with ssDNA-dsDNA junctions that mimic structural features of the replication fork and transcriptional R-loops. We find that when RPA is tightly bound to the ssDNA overhang of junction DNA substrates, base excision by hUNG2 is strongly biased toward uracils located 21 bp or less from the ssDNA-dsDNA junction. In the absence of RPA, hUNG2 still showed an 8-fold excision bias …


Considerations For Best Practices In Studies Of Fiber Or Other Dietary Components And The Intestinal Microbiome, David M. Klurfeld, Cindy D. Davis, Robert W. Karp, Emma Allen-Vercoe, Eugene B. Chang, Benoit Chassaing, George C. Fahey Jr, Bruce R. Hamaker, Hannah D. Holscher, Johanna W. Lampe, Andre Marette, Eric Martens, Stephen J. O'Keefe, Devin J. Rose, Maria Saarela, Barbara O. Schneeman, Joanne L. Slavin, Justin L. Sonnenburg, Kelly S. Swanson, Gary D. Wu, Christopher J. Lynch Aug 2018

Considerations For Best Practices In Studies Of Fiber Or Other Dietary Components And The Intestinal Microbiome, David M. Klurfeld, Cindy D. Davis, Robert W. Karp, Emma Allen-Vercoe, Eugene B. Chang, Benoit Chassaing, George C. Fahey Jr, Bruce R. Hamaker, Hannah D. Holscher, Johanna W. Lampe, Andre Marette, Eric Martens, Stephen J. O'Keefe, Devin J. Rose, Maria Saarela, Barbara O. Schneeman, Joanne L. Slavin, Justin L. Sonnenburg, Kelly S. Swanson, Gary D. Wu, Christopher J. Lynch

Food for Health: Publications

Considerations for best practices in studies of fiber or other dietary components and the intestinal microbiome. Am J Physiol Endocrinol Metab 315: E1087–E1097, 2018. First published August 21, 2018; doi:10.1152/ajpendo.00058.2018.—A 2-day workshop organized by the National Institutes of Health and U.S. Department of Agriculture included 16 presentations focused on the role of diet in alterations of the gastrointestinal microbiome, primarily that of the colon. Although thousands of research projects have been funded by U.S. federal agencies to study the intestinal microbiome of humans and a variety of animal models, only a minority addresses dietary effects, and a small subset is …


Integrative Signaling Of Mitochondria, Trpa1 And Trpv1 In Vagal Neurons, Katherine Stanford Aug 2018

Integrative Signaling Of Mitochondria, Trpa1 And Trpv1 In Vagal Neurons, Katherine Stanford

USF Tampa Graduate Theses and Dissertations

Sensory nerves detect conditions in the external and internal environment and permit behavioral and physiological responses to maintain homeostasis and ensure survival. As such, sensory nerves detect a wide variety of stimuli including heat, touch, pH, and vibration. The precise nature of these responses is dependent upon the initiating stimulus and site of activation. Potentially threatening stimuli (noxious heat, cellular damage, chemical irritants) activate nociceptive sensory nerves through the gating of ion channels expressed at sensory nerve terminals, thereby evoking defensive reflexes such as cough, watering eyes and limb withdrawal as well as sensations of pain or discomfort. While these …


Week Of August 20, 2018, New York Medical College Aug 2018

Uplc-Ms/Ms Analysis Of Dextromethorphan-O-Demethylation Kinetics In Rat Brain Microsomes, Barent N. Dubois, Reza Mehvar Aug 2018

Uplc-Ms/Ms Analysis Of Dextromethorphan-O-Demethylation Kinetics In Rat Brain Microsomes, Barent N. Dubois, Reza Mehvar

Pharmacy Faculty Articles and Research

Formation of dextrorphan (DXT) from dextromethorphan (DXM) has been widely used to assess cytochrome P450 2D (CYP2D) activity. Additionally, the kinetics of CYP2D activity have been well characterized in the liver microsomes. However, studies in brain microsomes are limited due to the lower microsomal content and abundance of CYP2D in the brain relative to the liver. In the present study, we developed a micro-scale enzymatic incubation method, coupled with a sensitive UPLC-MS/MS assay for the quantitation of the rate of DXT formation from DXM in brain microsomes. Rat brain microsomes were incubated with different concentrations of DXM for various times. …


An Evaluation Of The Use Of A Clinical Research Data Warehouse And I2b2 Infrastructure To Facilitate Replication Of Research, Bret Gardner Aug 2018

An Evaluation Of The Use Of A Clinical Research Data Warehouse And I2b2 Infrastructure To Facilitate Replication Of Research, Bret Gardner

Theses & Dissertations

Replication of clinical research is requisite for forming effective clinical decisions and guidelines. While rerunning a clinical trial may be unethical and prohibitively expensive, the adoption of EHRs and the infrastructure for distributed research networks provide access to clinical data for observational and retrospective studies. Herein I demonstrate a means of using these tools to validate existing results and extend the findings to novel populations. I describe the process of evaluating published risk models as well as local data and infrastructure to assess the replicability of the study. I use an example of a risk model unable to be replicated …


Aged Murine Hematopoietic Stem Cells Drive Aging-Associate Immune Remodeling, Hanna Leins, Medhanie Mulaw, Karina Eiwen, Vadim Sakk, Ying Liang, Michael Denkinger, Hartmut Geiger, Reinhold Schirmbeck Aug 2018

Aged Murine Hematopoietic Stem Cells Drive Aging-Associate Immune Remodeling, Hanna Leins, Medhanie Mulaw, Karina Eiwen, Vadim Sakk, Ying Liang, Michael Denkinger, Hartmut Geiger, Reinhold Schirmbeck

Toxicology and Cancer Biology Faculty Publications

Aging-associated remodeling of the immune system impairs its functional integrity and contributes to increased morbidity and mortality in the elderly. Aging of hematopoietic stem cells (HSCs), from which all cells of the adaptive immune system ultimately originate, might play a crucial role in the remodeling of the aged immune system. We recently reported that aging of HSCs is, in part, driven by elevated activity of the small RhoGTPase Cdc42 and that aged HSCs can be rejuvenated in vitro by inhibition of the elevated Cdc42 activity in aged HSCs with the pharmacological compound CASIN. To study the quality of immune systems …


A-Type Kv Channels In Dorsal Root Ganglion Neurons: Diversity, Function, And Dysfunction, Benjamin M. Zemel, David M. Ritter, Manuel Covarrubias, Tanziyah Muqeem Aug 2018

A-Type Kv Channels In Dorsal Root Ganglion Neurons: Diversity, Function, And Dysfunction, Benjamin M. Zemel, David M. Ritter, Manuel Covarrubias, Tanziyah Muqeem

Department of Neuroscience Faculty Papers

A-type voltage-gated potassium (Kv) channels are major regulators of neuronal excitability that have been mainly characterized in the central nervous system. By contrast, there is a paucity of knowledge about the molecular physiology of these Kv channels in the peripheral nervous system, including highly specialized and heterogenous dorsal root ganglion (DRG) neurons. Although all A-type Kv channels display pore-forming subunits with similar structural properties and fast inactivation, their voltage-, and time-dependent properties and modulation are significantly different. These differences ultimately determine distinct physiological roles of diverse A-type Kv channels, and how their dysfunction might contribute to neurological disorders. The importance …


The Guanylate Cyclase C-Cgmp Signaling Axis Opposes Intestinal Epithelial Injury And Neoplasia., Jeffrey A. Rappaport, Scott A. Waldman Aug 2018

The Guanylate Cyclase C-Cgmp Signaling Axis Opposes Intestinal Epithelial Injury And Neoplasia., Jeffrey A. Rappaport, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Guanylate cyclase C (GUCY2C) is a transmembrane receptor expressed on the luminal aspect of the intestinal epithelium. Its ligands include bacterial heat-stable enterotoxins responsible for traveler's diarrhea, the endogenous peptide hormones uroguanylin and guanylin, and the synthetic agents, linaclotide, plecanatide, and dolcanatide. Ligand-activated GUCY2C catalyzes the synthesis of intracellular cyclic GMP (cGMP), initiating signaling cascades underlying homeostasis of the intestinal epithelium. Mouse models of GUCY2C ablation, and recently, human populations harboring GUCY2C mutations, have revealed the diverse contributions of this signaling axis to epithelial health, including regulating fluid secretion, microbiome composition, intestinal barrier integrity, epithelial renewal, cell cycle progression, responses …


Week Of August 6, 2018, New York Medical College Aug 2018

Autotaxin-Lpa Signaling Contributes To Obesity-Induced Insulin Resistance In Muscle And Impairs Mitochondrial Metabolism, Kenneth D'Souza, Carine Nzirorera, Andrew M. Cowie, Geena P. Varghese, Purvi Trivedi, Thomas O. Eichmann, Dipsikha Biswas, Mohamed Touaibia, Andrew J. Morris, Vassilis Aidinis, Daniel A. Kane, Thomas Pulinilkunnil, Petra C. Kienesberger Aug 2018

Autotaxin-Lpa Signaling Contributes To Obesity-Induced Insulin Resistance In Muscle And Impairs Mitochondrial Metabolism, Kenneth D'Souza, Carine Nzirorera, Andrew M. Cowie, Geena P. Varghese, Purvi Trivedi, Thomas O. Eichmann, Dipsikha Biswas, Mohamed Touaibia, Andrew J. Morris, Vassilis Aidinis, Daniel A. Kane, Thomas Pulinilkunnil, Petra C. Kienesberger

Internal Medicine Faculty Publications

Autotaxin (ATX) is an adipokine that generates the bioactive lipid, lysophosphatidic acid (LPA). ATX-LPA signaling has been implicated in diet-induced obesity and systemic insulin resistance. However, it remains unclear whether the ATX-LPA pathway influences insulin function and energy metabolism in target tissues, particularly skeletal muscle, the major site of insulin-stimulated glucose disposal. The objective of this study was to test whether the ATX-LPA pathway impacts tissue insulin signaling and mitochondrial metabolism in skeletal muscle during obesity. Male mice with heterozygous ATX deficiency (ATX+/−) were protected from obesity, systemic insulin resistance, and cardiomyocyte dysfunction following high-fat high-sucrose (HFHS) feeding. …


An Eqtl Landscape Of Kidney Tissue In Human Nephrotic Syndrome., Christopher E. Gillies, Rosemary Putler, Rajasree Menon, Edgar Otto, Kalyn Yasutake, Viji Nair, Paul Hoover, David Lieb, Shuqiang Li, Sean Eddy, Damian Fermin, Michelle T. Mcnulty, Nephrotic Syndrome Study Network (Neptune), Nir Hacohen, Krzysztof Kiryluk, Matthias Kretzler, Xiaoquan Wen, Matthew G. Sampson, Tarak Srivastava Aug 2018

An Eqtl Landscape Of Kidney Tissue In Human Nephrotic Syndrome., Christopher E. Gillies, Rosemary Putler, Rajasree Menon, Edgar Otto, Kalyn Yasutake, Viji Nair, Paul Hoover, David Lieb, Shuqiang Li, Sean Eddy, Damian Fermin, Michelle T. Mcnulty, Nephrotic Syndrome Study Network (Neptune), Nir Hacohen, Krzysztof Kiryluk, Matthias Kretzler, Xiaoquan Wen, Matthew G. Sampson, Tarak Srivastava

Manuscripts, Articles, Book Chapters and Other Papers

Expression quantitative trait loci (eQTL) studies illuminate the genetics of gene expression and, in disease research, can be particularly illuminating when using the tissues directly impacted by the condition. In nephrology, there is a paucity of eQTL studies of human kidney. Here, we used whole-genome sequencing (WGS) and microdissected glomerular (GLOM) and tubulointerstitial (TI) transcriptomes from 187 individuals with nephrotic syndrome (NS) to describe the eQTL landscape in these functionally distinct kidney structures. Using MatrixEQTL, we performed cis-eQTL analysis on GLOM (n = 136) and TI (n = 166). We used the Bayesian "Deterministic Approximation of Posteriors" (DAP) to fine-map …


The Role Of Developmental Timing Regulators In Progenitor Proliferation And Cell Fate Specification During Mammalian Neurogenesis, Jennifer S. Romer-Seibert Aug 2018

The Role Of Developmental Timing Regulators In Progenitor Proliferation And Cell Fate Specification During Mammalian Neurogenesis, Jennifer S. Romer-Seibert

Graduate School of Biomedical Sciences Theses and Dissertations

Developmental timing is a key aspect of tissue and organ formation in which distinct cell types are generated through a series of steps from common progenitors. These progenitors undergo specific changes in gene expression that signifies both a distinct progenitor type and developmental time point that thereby specifies a particular cell fate at that stage of development. The nervous system is an important setting for understanding developmental timing because different cell types are produced in a certain order and the switch from stem cells to progenitors requires precise timing and regulation. Notable examples of such regulatory molecules include the RNA-binding …


Inhibition Of Ribosome Biogenesis Through Genetic And Chemical Approaches, Leonid Anikin Aug 2018

Inhibition Of Ribosome Biogenesis Through Genetic And Chemical Approaches, Leonid Anikin

Graduate School of Biomedical Sciences Theses and Dissertations

In order to maintain the ability to generate proteins, proliferating cells must continuously generate ribosomes, designating up to 80% of their energy to ribosome biogenesis (RBG). RBG involves transcription of rDNA by RNA polymerases I (Pol I) and III (Pol III), expression of approximately 80 ribosomal proteins, and assembly of these components in a process referred to as ribosome maturation. During maturation, the Pol I transcribed 47S pre-rRNA undergoes a number of processing events, while simultaneously interacting with processing factors and ribosomal proteins that drive pre-ribosome assembly. Inhibition of RBG has become one of the pursued targets for cancer therapy …


Gender- And Region-Specific Changes In Estrogen Signaling In Aging Rat Brain Mitochondria, Christopher M. Evola, Tanner L. Hudson, Luping Huang, Adrian M. Corbett, Debra A. Mayes Aug 2018

Gender- And Region-Specific Changes In Estrogen Signaling In Aging Rat Brain Mitochondria, Christopher M. Evola, Tanner L. Hudson, Luping Huang, Adrian M. Corbett, Debra A. Mayes

Neuroscience, Cell Biology & Physiology Faculty Publications

Recently epidemiological studies suggest females lose neuroprotection from neurodegenerative diseases as they go through menopause. 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, gender, and brain region. …


Translational Repression Of Pre-Formed Cytokine-Encoding Mrna Prevents Chronic Activation Of Memory T Cells, Fiamma Salerno, Sander Engels, Maartje Van Den Biggelaar, Floris P.J. Van Alphen, Aurelie Guislain, Wanqi Zhao, Deborah L. Hodge, Sarah E. Bell, Jan Paul Medema, Marieke Von Lindern, Martin Turner, Howard A. Young, Monika C. Wolkers Aug 2018

Translational Repression Of Pre-Formed Cytokine-Encoding Mrna Prevents Chronic Activation Of Memory T Cells, Fiamma Salerno, Sander Engels, Maartje Van Den Biggelaar, Floris P.J. Van Alphen, Aurelie Guislain, Wanqi Zhao, Deborah L. Hodge, Sarah E. Bell, Jan Paul Medema, Marieke Von Lindern, Martin Turner, Howard A. Young, Monika C. Wolkers

United States Public Health Resources

Memory T cells are critical for the immune response to recurring infections. Their instantaneous reactivity to pathogens is empowered by the persistent expression of cytokine-encoding mRNAs. How the translation of proteins from pre-formed cytokine-encoding mRNAs is prevented in the absence of infection has remained unclear. Here we found that protein production in memory T cells was blocked via a 3′ untranslated region (3′ UTR)-mediated process. Germline deletion of AU-rich elements (AREs) in the Ifng-3′ UTR led to chronic cytokine production in memory T cells. This aberrant protein production did not result from increased expression and/or half-life of the mRNA. Instead, …


Syntaphilin Ubiquitination Regulates Mitochondrial Dynamics And Tumor Cell Movements., Jae Ho Seo, Ekta Agarwal, Kelly G. Bryant, M. Cecilia Caino, Eui Tae Kim, Andrew V. Kossenkov, Hsin-Yao Tang, Lucia R. Languino, Dmitry I. Gabrilovich, Andrew R. Cohen, David W. Speicher, Dario C. Altieri Aug 2018

Syntaphilin Ubiquitination Regulates Mitochondrial Dynamics And Tumor Cell Movements., Jae Ho Seo, Ekta Agarwal, Kelly G. Bryant, M. Cecilia Caino, Eui Tae Kim, Andrew V. Kossenkov, Hsin-Yao Tang, Lucia R. Languino, Dmitry I. Gabrilovich, Andrew R. Cohen, David W. Speicher, Dario C. Altieri

Department of Cancer Biology Faculty Papers

Syntaphilin (SNPH) inhibits the movement of mitochondria in tumor cells, preventing their accumulation at the cortical cytoskeleton and limiting the bioenergetics of cell motility and invasion. Although this may suppress metastasis, the regulation of the SNPH pathway is not well understood. Using a global proteomics screen, we show that SNPH associates with multiple regulators of ubiquitin-dependent responses and is ubiquitinated by the E3 ligase CHIP (or STUB1) on Lys111 and Lys153 in the microtubule-binding domain. SNPH ubiquitination did not result in protein degradation, but instead anchored SNPH on tubulin to inhibit mitochondrial motility and cycles of organelle fusion and fission, …


Cardiac Autonomic Neuropathy In Diabetes: A Predictor Of Cardiometabolic Events, Aaron I. Vinik, Carolina Casellini, Henri K. Parson, Sheri R. Colberg, Marie-Laure Nevoret Aug 2018

Cardiac Autonomic Neuropathy In Diabetes: A Predictor Of Cardiometabolic Events, Aaron I. Vinik, Carolina Casellini, Henri K. Parson, Sheri R. Colberg, Marie-Laure Nevoret

Human Movement Studies & Special Education Faculty Publications

Autonomic nervous system (ANS) imbalance manifesting as cardiac autonomic neuropathy in the diabetic population is an important predictor of cardiovascular events. Symptoms and signs of ANS dysfunction, such as resting heart rate elevations, diminished blood pressure responses to standing, and altered time and frequency domain measures of heart rate variability in response to deep breathing, standing, and the Valsalva maneuver, should be elicited from all patients with diabetes and prediabetes. With the recognition of the presence of ANS imbalance or for its prevention, a rigorous regime should be implemented with lifestyle modification, physical activity, and cautious use of medications that …


Effects Of Eicosapentaenoic Acid (Epa) On Mouse Endothelial Cell Health, Spencer C. Pageau Aug 2018

Effects Of Eicosapentaenoic Acid (Epa) On Mouse Endothelial Cell Health, Spencer C. Pageau

Masters Theses

Cardiovascular disease is the number one killer of adults in the US (~800,000 lives every year:1 in 3 deaths). Evidence suggests omega-3 fatty acids like eicosapentaenoic acid (EPA), found in fish oils, reduce the risk of developing cardiovascular diseases. Many of these diseases are caused by atherosclerotic plaque development in vessels due to endothelial cell damage initiating inflammatory responses. Recent work argues omega-3 fatty acids stimulate anti-inflammatory responses by binding to Free Fatty Acid (FFA) receptors. Inflammatory responses in endothelial cells alter the expression of many proteins that affect the function of those cells. In particular, gap junction protein (connexin: …


Overexpression Of Cyb5r3 And Nqo1, Two Nad+-Producing Enzymes, Mimics Aspects Of Caloric Restriction, Alberto Diaz-Ruiz, Michael Lanasa, Joseph Garcia, Hector Mora, Frances Fan, Alejandro Martin-Montalvo, Andrea Di Francesco, Miguel Calvo-Rubio, Andrea Salvador-Pascual, Miguel A. Aon, Kenneth W. Fishbein, Kevin J. Pearson, Jose Manuel Villalba, Placido Navas, Michel Bernier, Rafael De Cabo Aug 2018

Overexpression Of Cyb5r3 And Nqo1, Two Nad+-Producing Enzymes, Mimics Aspects Of Caloric Restriction, Alberto Diaz-Ruiz, Michael Lanasa, Joseph Garcia, Hector Mora, Frances Fan, Alejandro Martin-Montalvo, Andrea Di Francesco, Miguel Calvo-Rubio, Andrea Salvador-Pascual, Miguel A. Aon, Kenneth W. Fishbein, Kevin J. Pearson, Jose Manuel Villalba, Placido Navas, Michel Bernier, Rafael De Cabo

Pharmacology and Nutritional Sciences Faculty Publications

Calorie restriction (CR) is one of the most robust means to improve health and survival in model organisms. CR imposes a metabolic program that leads to increased stress resistance and delayed onset of chronic diseases, including cancer. In rodents, CR induces the upregulation of two NADH‐dehydrogenases, namely NAD(P)H:quinone oxidoreductase 1 (Nqo1) and cytochrome b5 reductase 3 (Cyb5r3), which provide electrons for energy metabolism. It has been proposed that this upregulation may be responsible for some of the beneficial effects of CR, and defects in their activity are linked to aging and several age‐associated diseases. However, …


Bayesian Analytical Approaches For Metabolomics : A Novel Method For Molecular Structure-Informed Metabolite Interaction Modeling, A Novel Diagnostic Model For Differentiating Myocardial Infarction Type, And Approaches For Compound Identification Given Mass Spectrometry Data., Patrick J. Trainor Aug 2018

Bayesian Analytical Approaches For Metabolomics : A Novel Method For Molecular Structure-Informed Metabolite Interaction Modeling, A Novel Diagnostic Model For Differentiating Myocardial Infarction Type, And Approaches For Compound Identification Given Mass Spectrometry Data., Patrick J. Trainor

Electronic Theses and Dissertations

Metabolomics, the study of small molecules in biological systems, has enjoyed great success in enabling researchers to examine disease-associated metabolic dysregulation and has been utilized for the discovery biomarkers of disease and phenotypic states. In spite of recent technological advances in the analytical platforms utilized in metabolomics and the proliferation of tools for the analysis of metabolomics data, significant challenges in metabolomics data analyses remain. In this dissertation, we present three of these challenges and Bayesian methodological solutions for each. In the first part we develop a new methodology to serve a basis for making higher order inferences in metabolomics, …


Deciphering The Role Of Human Arylamine N-Acetyltransferase 1 (Nat1) In Breast Cancer Cell Metabolism Using A Systems Biology Approach., Samantha Marie Carlisle Aug 2018

Deciphering The Role Of Human Arylamine N-Acetyltransferase 1 (Nat1) In Breast Cancer Cell Metabolism Using A Systems Biology Approach., Samantha Marie Carlisle

Electronic Theses and Dissertations

Background: Human arylamine N-acetyltransferase 1 (NAT1) is a phase II xenobiotic metabolizing enzyme found in almost all tissues. NAT1 can additionally hydrolyze acetyl-coenzyme A (acetyl-CoA) in the absence of an arylamine substrate. NAT1 expression varies inter-individually and is elevated in several cancers including estrogen receptor positive (ER+) breast cancers. Additionally, multiple studies have shown the knockdown of NAT1, by both small molecule inhibition and siRNA methods, in breast cancer cells leads to decreased invasive ability and proliferation and decreased anchorage-independent colony formation. However, the exact mechanism by which NAT1 expression affects cancer risk and progression remains unclear. Additionally, consequences …


Alpha-Amino Methylation And Acetylation Are Novel Regulators Of Myl9 Function., Christopher David Nevitt Aug 2018

Alpha-Amino Methylation And Acetylation Are Novel Regulators Of Myl9 Function., Christopher David Nevitt

Electronic Theses and Dissertations

Dysregulation of alpha-amino post-translational modifications (Nα-PTMs) is found in multiple cancers and developmental disorders. However, the exact roles Nα-PTMs play in regulating protein function remain poorly understood. I sought to clarify the role of Nα-methylation and Nα-acetylation in the regulation of Myosin Regulatory Light Chain 9 (MYL9). MYL9 is a key cytoskeletal regulator and transcription factor and is the first protein confirmed to undergo both Nα-methylation and Nα-acetylation. Through this work I revealed novel regulatory features of MYL9, while also presenting a framework by which to understand the coordinated regulation of proteins by Nα-methylation and Nα-acetylation. Nα-PTM selective mutants of …


Evaluation Of Endothelial Cell Responses To Elevated Glucose, Gabriella Sugerman Aug 2018

Evaluation Of Endothelial Cell Responses To Elevated Glucose, Gabriella Sugerman

Master's Theses

Developing a tissue-engineered Blood Vessel Mimic (BVM) to represent diabetic macrovascular disease could expedite design of new vascular devices specifically tailored to diabetic patients. In contribution toward this model, this thesis assessed Human Umbilical Vein Endothelial Cell (HUVEC) responses to high glucose conditions. Interleukin 6 (IL-6) and Cluster of Differentiation 36 (CD36) were selected to signify oxidative stress activity, a hallmark of diabetic macrovascular disease. Next, activity of potential reference genes B2M, HPRT1, and ACTB was assessed. All genes were found to exceed acceptable variability, so the E-ΔC T method of data analysis was selected. Next, cellular responses to high …


Review Of Karyotypic Data From Low Grade Glial Brain Tumors, Specifically Pilocytic Astrocytomas, And Correlation Of Genetic Aberrations With Tumor Recurrence., Linda D. Cooley, Scott C. Smith, Lisa Warren, Melissa Gener, Kevin Ginn, John Herriges Aug 2018

Review Of Karyotypic Data From Low Grade Glial Brain Tumors, Specifically Pilocytic Astrocytomas, And Correlation Of Genetic Aberrations With Tumor Recurrence., Linda D. Cooley, Scott C. Smith, Lisa Warren, Melissa Gener, Kevin Ginn, John Herriges

Posters

Abstract: Brain tumors are the most common solid tumor of childhood. Approximately 50% of pediatric CNS tumors are low grade gliomas (WHO grade I or II) and Pilocytic astrocytoma (PA) is the most common accounting for 33% of all gliomas in children 0-14 years and ~18% of all childhood brain tumors. Prognosis with this slow-growing tumor is excellent; 10 year overall survival of ~95%. However, event free survival averages ~50%. Patient age and extent of tumor resection are key prognostic factors; tumor location and size impact resection and outcome. Histopathological features indicate PA is a benign tumor and rarely are …