Biochemistry, Biophysics, and Structural Biology Commons^™

Letter From The Dean, Lalit Verma

Discovery, The Student Journal of Dale Bumpers College of Agricultural, Food and Life Sciences

No abstract provided.

Hmgb1 Mediates Endogenous Tlr2 Activation And Brain Tumor Regression, James Curtin, Naiyou Liu, Marianela Candolfi, Weidong Xiong, Hikmat Assi, Kader Yagiz, Matthew Edwards, Kathrin Michelsen, Kurt Kroeger, Chunyan Liu, Akm Ghulam Muhammad, Mary Clark, Moshe Arditi, Begonya Comin-Anduix, Antoni Ribas, Pedro Lowenstein, Maria Castro

Articles

BACKGROUND: Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor that carries a 5-y survival rate of 5%. Attempts at eliciting a clinically relevant anti-GBM immune response in brain tumor patients have met with limited success, which is due to brain immune privilege, tumor immune evasion, and a paucity of dendritic cells (DCs) within the central nervous system. Herein we uncovered a novel pathway for the activation of an effective anti-GBM immune response mediated by high-mobility-group box 1 (HMGB1), an alarmin protein released from dying tumor cells, which acts as an endogenous ligand for Toll-like receptor 2 (TLR2) signaling …

Transcriptional Regulation Of Cholesterol 24-Hydroxylase By Histone Deacetylase Inhibitors., Marjan Shafaati, Riona O'Driscoll, Ingemar Bjorkhem, Steve Meaney

Articles

The mechanistic basis for the tissue specific expression of cholesterol elimination pathways is poorly understood. To gain additional insight into this phenomenon we considered it of interest to investigate if epigenetic mechanisms are involved in the regulation of the brain-specific enzyme cholesterol 24-hydroxylase (CYP46A1), a key regulator of brain cholesterol elimination. We demonstrated a marked time-dependent derepression of the expression of CYP46A1, in response to treatment with the potent histone deacetylase (HDAC) inhibitor Trichostatin A. The pattern of expression of the genes in the genomic region surrounding CYP46A1 was found to be diametrically opposite in brain and liver. Intraperitoneal injection …

Pressure-Driven Transport Of Particles Through A Converging-Diverging Microchannel, Ye Ai, Sang W. Joo, Xiangchun Xuan, Shizhi Qian

Mechanical & Aerospace Engineering Faculty Publications

Pressure-driven transport of particles through a symmetric converging-diverging microchannel is studied by solving a coupled nonlinear system, which is composed of the Navier-Stokes and continuity equations using the arbitrary Lagrangian-Eulerian finite-element technique. The predicted particle translation is in good agreement with existing experimental observations. The effects of pressure gradient, particle size, channel geometry, and a particle's initial location on the particle transport are investigated. The pressure gradient has no effect on the ratio of the translational velocity of particles through a converging-diverging channel to that in the upstream straight channel. Particles are generally accelerated in the converging region and then …

Vibrational Spectroscopy Of Isotopically Labeled Indoles And Electron Transfer Involving Indole (Tryptophan) Radicals, Senghane Dominique Dieng

Theses, Dissertations and Culminating Projects

Vibrational spectroscopy of tryptophan can be used as a probe for local protein conformation and to study protein electron transfer. For the interpretation of the vibrational spectra, the proper assignment of the vibrational bands to normal modes is essential. We report the experimentally measured infrared and Raman spectra of tryptophan, indole and 3-methylindole as well as of several of their isotope substituted forms; tryptophan indole-d₅ and -¹⁵N₂, and indole 2-¹³C. The effect of the exchange of the indole NH to ND on the vibrational spectra of these molecules was also determined. The measurements …

Hydroxyl Radical Is Produced Via The Fenton Reaction In Submitochondrial Particles Under Oxidative Stress: Implications For Diseases Associated With Iron Accumulation, Carin Thomas, Melissa M. Mackey, Amy A. Diaz, David P. Cox

All Faculty Scholarship for the College of the Sciences

Mitochondrial dysfunction and reactive oxygen species (ROS) are often implicated in diseases involving oxidative stress and elevated iron. As mitochondria produce ATP by oxidative phosphorylation, ROS by-products are generated from the electron transport chain. Although superoxide and hydrogen peroxide have been thoroughly investigated, little evidence documents hydroxyl radical (HO•) production in mitochondria. In order to determine whether HO• is generated under oxidative stress conditions by a Fenton-type mechanism, bovine heart submitochondrial particles were examined for HO• in the presence and absence of iron ligands, antioxidant enzymes and HO• scavengers. HO• was measured as 2,3- and 2,5-dihydroxybenzoic acid (DHBA), using HPLC …

Crystal Structure Of Acivicin-Inhibited Γ-Glutamyltranspeptidase Reveals Critical Roles For Its C-Terminus In Autoprocessing And Catalysis, Kristin Williams, Sierra Cullati, Aaron Sand, Ekaterina I. Biterova, Joseph J. Barycki

Department of Biochemistry: Faculty Publications

Helicobacter pylori γ-glutamyltranspeptidase (HpGT) is a general γ-glutamyl hydrolase and a

demonstrated virulence factor. The enzyme confers a growth advantage to the bacterium, providing essential amino acid precursors by initiating the degradation of extracellular glutathione and glutamine. HpGT is a member of the N-terminal nucleophile (Ntn) hydrolase superfamily and undergoes autoprocessing to generate the active form of the enzyme. Acivicin is a widely used γ-glutamyltranspeptidase inhibitor that covalently modifies the enzyme, but its precise mechanism of action remains unclear. The time-dependent inactivation of HpGT exhibits a hyperbolic dependence on acivicin concentration with kmax = 0.033 ± 0.006 sec^{−1 …}

Comparative Efficacy Of Bioud To Other Commercially Available Arthropod Repellants Against The Ticks Amblyomma Americanum And Dermacentor Variabilis On Cotton Cloth, Brooke W. Bissinger, Jiwei Zhu, Charles S. Apperson, Daniel E. Sonenshine, D. Wesley Watson, R. Michael Roe

Biological Sciences Faculty Publications

BioUD is an arthropod repellent that contains the active ingredient 2-undecanone originally derived from wild tomato plants. Repellency of BioUD was compared with five commercially available arthropod repellents against the ticks Amblyomma americanum (L.) and Dermacentor variabilis Say in two-choice bioassays on treated versus untreated cotton cheesecloth. Overall mean percentage repellency against both species was greatest for and did not differ significantly between BioUD (7.75% 2-undecanone) and products containing 98.1% DEET, 19.6% IR3535, and 30% oil of lemon eucalyptus. Products containing 5% and 15% Picaridin and 0.5% permethrin were also repellent compared with untreated controls but to a lesser degree …

Computational Studies On R67 Dihydrofolate Reductase: An Investigation Into Its Unique Binding Patterns, Chuanyin Shi

Theses and Dissertations in Biomedical Sciences

R67 dihydrofolate reductase (R67 DHFR) is a plasmid encoded enzyme which catalyzes the reduction of dihydrofolate (DHF) to tetrahydrofolate (THF) using NADPH as a cofactor. R67 DHFR is a homo-tetramer and D2 symmetric. It contains only one active site, which spans the central channel of the enzyme. The active site can bind either two reactants (DHF), two cofactors (NADPH) or one of each (NADPH/DHF), which is the productive ternary complex (i.e. the complex which yields product). In order to favor formation of the productive complex, this enzyme exhibits binding cooperativity. Unlike other allosteric enzymes which achieve binding cooperativity through conformational …

Substrate And Regulation Of Mitochondrial Μ-Calpain, Aashish Joshi

University of Kentucky Doctoral Dissertations

μ -Calpain is localized to the mitochondrial intermembrane space. Apoptosisinducing factor (AIF), which executes caspase-independent cell death, is also localized to the mitochondrial intermembrane space. Following processing at the N-terminus, AIF becomes truncated (tAIF) and is released from mitochondria. The protease responsible for AIF processing has not been established. The same submitochondrial localization of mitochondrial μ-calpain and AIF gives support to the hypothesis that mitochondrial μ-calpain may be responsible for processing AIF. Atractyloside-induced tAIF release in rat liver mitochondria was inhibited by cysteine protease inhibitor MDL28170, but not by calpain inhibitors PD150606 or calpastatin. Moreover, μ-calpain immunoreactivity was difficult to …

Targeting The Fatty Acid Transport Proteins (Fatp) To Understand The Mechanisms Linking Fatty Acid Transport To Metabolism, Paul N. Black, Angel Sandoval, Elsa Arias-Barrau, Concetta C. Dirusso

Department of Biochemistry: Faculty Publications

One principal process driving fatty acid transport is vectorial acylation, where fatty acids traverse the membrane concomitant with activation to CoA thioesters. Current evidence is consistent with the proposal that specific fatty acid transport (FATP) isoforms alone or in concert with specific long chain acyl CoA synthetase (Acsl) isoforms function to drive this energy-dependent process. Understanding the details of vectorial acylation is of particular importance as disturbances in lipid metabolism many times leads to elevated levels of circulating free fatty acids, which in turn increases fatty acid internalization and ectopic accumulation of triglycerides. This is associated with changes in fatty …

Glucose Promotes Stress Resistance In The Fungal Pathogen Candida Albicans, Alexandra Rodaki, Iryna M. Bohovych, Brice Enjalbert, Tim Young, Frank C. Odds, Neil A.R. Gow, Alistair J.P. Brown

Department of Biochemistry: Faculty Publications

Metabolic adaptation, and in particular the modulation of carbon assimilatory pathways during disease progression, is thought to contribute to the pathogenicity of Candida albicans. Therefore, we have examined the global impact of glucose upon the C. albicans transcriptome, testing the sensitivity of this pathogen to wide-ranging glucose levels (0.01, 0.1, and 1.0%). We show that, like Saccharomyces cerevisiae, C. albicans is exquisitely sensitive to glucose, regulating central metabolic genes even in response to 0.01% glucose. This indicates that glucose concentrations in the bloodstream (approximate range 0.05–0.1%) have a significant impact upon C. albicans gene regulation. However, in contrast …

A Role For The Atp7a Copper-Transporting Atpase In Macrophage Bactericidal Activity, Carine White, Jaekwon Lee, Taiho Kambe, Kevin Fritsche, Michael J. Petris

Department of Biochemistry: Faculty Publications

Copper is an essential micronutrient that is necessary for healthy immune function. This requirement is underscored by an increased susceptibility to bacterial infection in copper-deficient animals; however, a molecular understanding of its importance in immune defense is unknown. In this study, we investigated the effect of proinflammatory agents on copper homeostasis in RAW264.7 macrophages. Interferon-γ was found to increase expression of the high affinity copper importer, CTR1, and stimulate copper uptake. This was accompanied by copper-stimulated trafficking of the ATP7A copper exporter from the Golgi to vesicles that partially overlapped with phagosomal compartments. Silencing of ATP7A expression attenuated bacterial killing, …

Copper Transport Activity Of Yeast Ctr1 Is Down-Regulated Via Its C Terminus In Response To Excess Copper, Xiaobin Wu, Devis Sinani, Heejeong Kim, Jaekwon Lee

Department of Biochemistry: Faculty Publications

Copper is an essential yet toxic trace element. The Ctr1 family of proteins plays a critical role for copper uptake in eukaryotes. However, the mechanisms of action of Ctr1 are largely unknown. Our previous data demonstrated that copper transport induces conformational changes in the cytosolic C terminus of the yeast Saccharomyces cerevisiae Ctr1. To define the physiological significance of this molecular event and gain better insights into the mechanism of Ctr1-mediated copper uptake, we have characterized the functional roles of the Ctr1 C terminus.ACtr1 mutant lacking the entire C-terminal cytosolic tail is functional in high affinity copper uptake; however, yeast …

Contribution Of Impaired Myocardial Insulin Signaling To Mitochondrial Dysfunction And Oxidative Stress In The Heart, Sihem Boudina, Heiko Bugger, Sandra Sena, Brian T. O'Neill, Vlad G. Zaha, Olesya Ilkun, Jordan J. Wright, Pradip K. Mazumber, Eric Palfreyman, Timothy J. Tidwell, Heather Theobald, Oleh Khalimonchuk, Benjamin Wayment, Xiaoming Sheng, Kenneth J. Rodnick, Ryan Centini, Dong Chen, Sheldon E. Litwin, Bart E. Weimer, E. Dale Abel

Department of Biochemistry: Faculty Publications

Background—Diabetes-associated cardiac dysfunction is associated with mitochondrial dysfunction and oxidative stress, which may contribute to LV dysfunction. The contribution of altered myocardial insulin action, independently of associated changes in systemic metabolism is incompletely understood. The present study tested the hypothesis that perinatal loss of insulin signaling in the heart impairs mitochondrial function.

Methods and Results—In 8-week-old mice with cardiomyocyte deletion of insulin receptors (CIRKO), inotropic reserves were reduced and mitochondria manifested respiratory defects for pyruvate that was associated with proportionate reductions in catalytic subunits of pyruvate dehydrogenase. Progressive age-dependent defects in oxygen consumption and ATP synthesis with the substrates glutamate …

Sdh5, A Gene Required For Flavination Of Succinate Dehydrogenase, Is Mutated In Paraganglioma, Huai-Xiang Hao, Oleh Khalimonchuk, Margit Schraders, Noah Dephoure, Jean-Pierre Bayley, Henricus Kunst, Peter Devilee, Cor W.R.J. Cremers, Joshua D. Schiffman, Brandon G. Bentz, Steven P. Gygi, Dennis R. Winge, Hannie Kremer, Jared Rutter

Department of Biochemistry: Faculty Publications

Mammalian mitochondria contain about 1100 proteins, nearly 300 of which are uncharacterized. Given the well-established role of mitochondrial defects in human disease, functional characterization of these proteins may shed new light on disease mechanisms. Starting with yeast as a model system, we investigated an uncharacterized but highly conserved mitochondrial protein (named here Sdh5). Both yeast and human Sdh5 interact with the catalytic subunit of the succinate dehydrogenase (SDH) complex, a component of both the electron transport chain and the tricarboxylic acid cycle. Sdh5 is required for SDH-dependent respiration and for Sdh1 flavination (incorporation of the flavin adenine dinucleotide cofactor). Germline …

Chemchains: A Platform For Simulation And Analysis Of Biochemical Networks Aimed To Laboratory Scientists, Tomáš Helikar, Jim A. Rogers

Department of Biochemistry: Faculty Publications

Background: New mathematical models of complex biological structures and computer simulation software allow modelers to simulate and analyze biochemical systems in silico and form mathematical predictions. Due to this potential predictive ability, the use of these models and software has the possibility to compliment laboratory investigations and help refine, or even develop, new hypotheses. However, the existing mathematical modeling techniques and simulation tools are often difficult to use by laboratory biologists without training in high-level mathematics, limiting their use to trained modelers.

Results: We have developed a Boolean network-based simulation and analysis software tool, ChemChains, which combines the advantages of …

Ulk-Atg13-Fip200 Complexes Mediate Mtor Signaling To The Autophagy Machinery, Chang Hwa Jung, Chang Bong Jun, Seung-Hyun Ro, Young-Mi Kim, Neil Michael Otto, Jing Cao, Mondira Kundu, Do-Hyung Kim

Department of Biochemistry: Faculty Publications

Autophagy, the starvation-induced degradation of bulky cytosolic components, is up-regulated in mammalian cells when nutrient supplies are limited. Although mammalian target of rapamycin (mTOR) is known as the key regulator of autophagy induction, the mechanism by which mTOR regulates autophagy has remained elusive. Here, we identify that mTOR phosphorylates a mammalian homologue of Atg13 and the mammalian Atg1 homologues ULK1 and ULK2. The mammalian Atg13 binds both ULK1 and ULK2 and mediates the interaction of the ULK proteins with FIP200. The binding of Atg13 stabilizes and activates ULK and facilitates the phosphorylation of FIP200 by ULK, whereas knockdown of Atg13 …

Editorial: Dietary Lipid Absorption, Concetta Dirusso, Paul N. Black

Department of Biochemistry: Faculty Publications

The composition of dietary fat influences tissue fatty acid composition, which in turn impacts cellular function through a number of different processes. This includes changes in signaling, lipid metabolism, and transcriptional activities that normally function to maintain intracellular fatty acid homeostasis. The consumption of high levels of dietary fat in excess of caloric expenditure is linked with obesity and the disruption of normal homeostatic mechanisms governing lipid metabolism. Data from the Centers for Disease Control and Prevention show that obesity (defined as a BMI≥30) represents a considerable health concern in the United States. Of particular note is that for adult …

Analysis Of N-Linked Oligosaccharides Of Prostate-Specific Antigen And Prostatic Acid Phosphatase In Prostatic Fluids, Krista Yaudes White

Theses and Dissertations in Biomedical Sciences

Presently, prostate cancer is the most common cancer afflicting men in the United States, with serum PSA being the "gold standard" protein biomarker used in the clinic for detecting and diagnosing prostate cancer. Nonetheless, serum PSA levels can also be elevated in non-cancerous conditions as well, such as benign prostatic hyperplasia (BPH). Due to this overlap, many unnecessary biopsies and radical prostatectomies occur, leading to patient distress. Despite recent advances to clinical assays which consider other clinical parameters, there is still a great need for improved clinical detection methodologies for prostate cancer, including improved biomarkers. Therefore, this research project aims …

Protection Of Macrophages J774a.1 By Purine Nucleoside Analogues From Bacillus Anthracis Mediated Necrosis, Zadkiel R. Alvarez

UNLV Theses, Dissertations, Professional Papers, and Capstones

Eight years after the lamentable anthrax attacks, major scientific effort continues to be done, in order to stop imminent acts of bioterrorism. Innovative ways of therapy against the anthrax disease are being investigated. B. anthracis, the etiological agent of the infection, has a dormant stage in its life cycle known as the endospore. When conditions become favorable spores germinate, transforming into vegetative bacteria. In inhalational anthrax, the most fatal manifestation of the disease, spores enter the organism through the respiratory track, and are phagocytosized by alveolar macrophages of the lungs. Spores are able to sense nutrient availability, activating their germination …

Arbuscular Mycorrhizal Fungi: Factors Affecting Soil Organic Matter Storage, Carl Lee Rosier

Graduate Student Theses, Dissertations, & Professional Papers

Arbuscular mycorrhizal fungi (AMF) are soil fungi forming symbiotic associations with majority of land plants. AMF alter soil organic matter (SOM) directly through stabilization of soil aggregates and indirectly providing a path in which plant fixed C02 is transferred below-ground. Understanding contributions of AMF to SOM via protein production and stabilization of soil aggregates will greatly aid our understanding of soil carbon sequestration, nutrient cycling and mitigation of soil erosion. The work presented in chapter 2 challenges the glomalin extraction process and assesses the accuracy of the Bradford and monoclonal-antibody ELISA detection methods. My results clarify the contribution of glomalin …

Laser-Induced Photon-Branched Chain Reaction In A Chemically-Active Gas-Dispersed Medium, Thomas George, Renat Letfullin, Galen Duree

Chemistry & Biochemistry Faculty Works

A promising avenue in the development of high-energy pulsed chemical HF/DF lasers and amplifiers is the utilization of a photon-branched chain reaction initiated in a two-phase active medium, that is, a medium containing a laser working gas and ultradispersed passivated metal particles. These particles are evaporated under the action of IR laser radiation which results in the appearance of free atoms, their diffusion into the gas, and the development of a photon-branching chain process, which involves photons as both reactants and products. The key obstacle here is the formation of a relatively large volume (in excess of 10^3 cm^3) of …

Structure And Dynamics Of Metalloproteins In Live Cells, Jeremy D. Cook, James E. Penner-Hahn, Timothy L. Stemmler

Biochemistry and Molecular Biology Faculty Publications

X-ray absorption spectroscopy (XAS) has emerged as one of the premier tools for investigating the structure and dynamic properties of metals in cells and in metal containing biomolecules. Utilizing the high flux and broad energy range of X-rays supplied by synchrotron light sources, one can selectively excite core electronic transitions in each metal. Spectroscopic signals from these electronic transitions can be used to dissect the chemical architecture of metals in cells, in cellular components and in biomolecules at varying degrees of structural resolution. With the development of ever-brighter X-ray sources, X-ray methods have grown into applications that can be utilized …

The Effect Of Oxidant And The Non-Oxidant Alteration Of Cellular Thiol Concentration On The Formation Of Protein Mixed-Disulfides In Hek 293 Cells, Jasen Lee Gilge, Michael Fisher, Yuh-Cherng Chai

Chemistry

Cellular molecules possess various mechanisms in responding to oxidant stress. In terms of protein responses, protein S-glutathionylation is a unique post-translational modification of protein reactive cysteines forming disulfides with glutathione molecules. This modification has been proposed to play roles in antioxidant, regulatory and signaling in cells under oxidant stress. Recently, the increased level of protein S-glutathionylation has been linked with the development of diseases. In this report, specific S-glutathionylated proteins were demonstrated in human embryonic kidney 293 cells treated with two different oxidative reagents: diamide and hydrogen peroxide. Diamide is a chemical oxidizing agent whereas hydrogen peroxide is a physiological …

Towards The Total Synthesis Of Thioviridamide: Thiyl Radical Approach To The Beta-Thioenamide Linkage Formation, Jung-Hoon Kang

Theses and Dissertations

We developed an approach to the β-thioenamide linkage contained in the S-(2-aminovinyl)cysteine (avCys) residue of thioviridamide.1,2 Kinetic and thermodynamic control of radical additions of thiols to ynamides were studied for the formation of β-thioenamide linkage. Thiyl radicals are electrophilic and ynamides are electron-rich alkynes. This complementary polarity of the radical and acceptor increases the likelihood of a successful radical addition reaction. Because little is known about these types of compounds (β-thioenamides), we were unsure what kinds of yields and stereoselectivities (cis vs. trans) to expect. The adduct stability is another issue to consider. Fortunately, under typical radical addition conditions, the …

Three-Dimensional Microfluidic Devices Fabricated In Layered Paper And Tape, Andres W. Martinez, Scott T. Phillips, George M. Whitesides

Chemistry and Biochemistry

This article describes a method for fabricating 3D microfluidic devices by stacking layers of patterned paper and double-sided adhesive tape. Paper-based 3D microfluidic devices have capabilities in microfluidics that are difficult to achieve using conventional open-channel microsystems made from glass or polymers. In particular, 3D paper-based devices wick fluids and distribute microliter volumes of samples from single inlet points into arrays of detection zones (with numbers up to thousands). This capability makes it possible to carry out a range of new analytical protocols simply and inexpensively (all on a piece of paper) without external pumps. We demonstrate a prototype 3D …

Sinorhizobium Meliloti, A Bacterium Lacking The Autoinducer-2 (Ai-2) Synthase, Responds To Ai-2 Supplied By Other Bacteria, C. S. Pereira, J. R. Mcauley, M. E. Taga, K. B. Xavier, Stephen T. Miller

Chemistry & Biochemistry Faculty Works

Many bacterial species respond to the quorum-sensing signal autoinducer-2 (AI-2) by regulating different niche-specific genes. Here, we show that Sinorhizobium meliloti, a plant symbiont lacking the gene for the AI-2 synthase, while not capable of producing AI-2 can nonetheless respond to AI-2 produced by other species. We demonstrate that S. meliloti has a periplasmic binding protein that binds AI-2. The crystal structure of this protein (here named SmlsrB) with its ligand reveals that it binds (2R,4S)-2-methyl-2,3,3,4-tetrahydroxytetrahydrofuran (R-THMF), the identical AI-2 isomer recognized by LsrB of Salmonella typhimurium. The gene encoding SmlsrB is in an operon with orthologues of the lsr …

Evidence Of A Novel Rna Secondary Structure In The Coding Region Of Hiv-1 Pol Gene., Qi Wang, Ian Barr, Feng Guo, Christopher Lee

Natural Sciences and Mathematics | Faculty Scholarship

RNA secondary structures play several important roles in the human immunodeficiency virus (HIV) life cycle. To assess whether RNA secondary structure might affect the function of the HIV protease and reverse transcriptase genes, which are the main targets of anti-HIV drugs, we applied a series of different computational approaches to detect RNA secondary structures, including thermodynamic RNA folding predictions, synonymous variability analysis, and covariance analysis. Each method independently revealed strong evidence of a novel RNA secondary structure at the junction of the protease and reverse transcriptase genes, consisting of a 107-nucleotide region containing three stems, A, B, and C. First, …

Comparison Of Electrically Mediated And Liposome-Complexed Plasmid Dna Delivery To The Skin, Loree C. Heller, Mark J. Jaroszeski, Domenico Coppola, Richard Heller

Bioelectrics Publications

BACKGROUND: Electroporation is an established technique for enhancing plasmid delivery to many tissues in vivo, including the skin. We have previously demonstrated efficient delivery of plasmid DNA to the skin utilizing a custom-built four-plate electrode. The experiments described here further evaluate cutaneous plasmid delivery using in vivo electroporation. Plasmid expression levels are compared to those after liposome mediated delivery.

METHODS: Enhanced electrically-mediated delivery, and less extensively, liposome complexed delivery, of a plasmid encoding the reporter luciferase was tested in rodent skin. Expression kinetics and tissue damage were explored as well as testing in a second rodent model.

RESULTS: Experiments …