Digital Commons Network^™

Adar2-Dependent Rna Editing Of Glur2 Is Involved In Thiamine Deficiency-Induced Alteration Of Calcium Dynamics, Shuchen Lee, Guang Yang, Yue Yong, Ying Liu, Liyun Zhao, Jing Xu, Xiaomin Zhang, Yanjie Wan, Chun Feng, Zhiqin Fan, Yong Liu, Jia Luo, Zun-Ji Ke

Internal Medicine Faculty Publications

BACKGROUND: Thiamine (vitamin B1) deficiency (TD) causes mild impairment of oxidative metabolism and region-selective neuronal loss in the central nervous system (CNS). TD in animals has been used to model aging-associated neurodegeneration in the brain. The mechanisms of TD-induced neuron death are complex, and it is likely multiple mechanisms interplay and contribute to the action of TD. In this study, we demonstrated that TD significantly increased intracellular calcium concentrations [Ca2+]i in cultured cortical neurons.

RESULTS: TD drastically potentiated AMPA-triggered calcium influx and inhibited pre-mRNA editing of GluR2, a Ca2+-permeable subtype of AMPA receptors. The Ca2+ permeability of GluR2 is regulated …

Networks Of European Cities In Worlds Of Global Economic And Environmental Change, Stanley D. Brunn, Lomme Devriendt, Andrew Boulton, Ben Derudder, Frank Witlox

Geography Faculty Publications

Geographers have a long tradition of classifying cities using a number of criteria. Population size, industrial production, capital city functions, airline connections, sites of sporting events and major headquarters and banks are among them. While these studies are useful in looking at cities in an economy and population at a given point of time, they are less useful in assessing rapidly occurring changes within a regional or global system. Our research represents a new approach to classify cities and urban systems; we use the volume and networks/linkages or flows associated with electronic Information or “Knowledge worlds.” We argue that in …

Leishmania Major Survival In Selective Phlebotomus Papatasi Sand Fly Vector Requires A Specific Scg-Encoded Lipophosphoglycan Galactosylation Pattern, Deborah E. Dobson, Shaden Kamhawi, Phillip Lawyer, Salvatore J. Turco, Stephen M. Beverley, David L. Sacks

Molecular and Cellular Biochemistry Faculty Publications

Phlebotomine sand flies that transmit the protozoan parasite Leishmania differ greatly in their ability to support different parasite species or strains in the laboratory: while some show considerable selectivity, others are more permissive. In "selective" sand flies, Leishmania binding and survival in the fly midgut typically depends upon the abundant promastigote surface adhesin lipophosphoglycan (LPG), which exhibits species- and strain-specific modifications of the dominant phosphoglycan (PG) repeat units. For the "selective" fly Phlebotomus papatasi PpapJ, side chain galactosyl-modifications (scGal) of PG repeats play key roles in parasite binding. We probed the specificity and properties of this scGal-LPG PAMP (Pathogen Associated …

Intestinal Epithelial Serum Amyloid A Modulates Bacterial Growth In Vitro And Pro-Inflammatory Responses In Mouse Experimental Colitis, Erik R.M. Eckhardt, Jassir Witta, Jian Zhong, Razvan Arsenescu, Violeta Arsenescu, Yu Wang, Sarbani Ghoshal, Marcielle C. De Beer, Frederick C. De Beer, Willem J.S. De Villiers

Internal Medicine Faculty Publications

BACKGROUND: Serum Amyloid A (SAA) is a major acute phase protein of unknown function. SAA is mostly expressed in the liver, but also in other tissues including the intestinal epithelium. SAA reportedly has anti-bacterial effects, and because inflammatory bowel diseases (IBD) result from a breakdown in homeostatic interactions between intestinal epithelia and bacteria, we hypothesized that SAA is protective during experimental colitis.

METHODS: Intestinal SAA expression was measured in mouse and human samples. Dextran sodium sulfate (DSS) colitis was induced in SAA 1/2 double knockout (DKO) mice and in wildtype controls. Anti-bacterial effects of SAA1/2 were tested in intestinal epithelial …

Aminopeptidases Do Not Directly Degrade Tau Protein, K. Martin Chow, Hanjun Guan, Louis B. Hersh

Molecular and Cellular Biochemistry Faculty Publications

BACKGROUND: Tau hyperphosphorylation and aggregation to form intracellular neurofibrillar tangles is prevalent in a number of tauopathies. Thus there is current interest in the mechanisms involved in Tau clearance. It was recently reported that Tau can be degraded by an aminopeptidase known as the puromycin sensitive aminopeptidase (PSA). Until now PSA has been reported to only cleave peptides, with the largest reported substrates having 30-50 amino acids. We have studied this unique PSA cleavage reaction using a number of different PSA preparations.

RESULTS: An N-terminally His tagged-PSA was expressed and purified from Sf9 insect cells. Although this PSA preparation cleaved …

Translation Elongation Factor 1a Facilitates The Assembly Of The Tombusvirus Replicase And Stimulates Minus-Strand Synthesis, Zhenghe Li, Judit Pogany, Steven Tupman, Anthony M. Esposito, Terri Goss Kinzy, Peter D. Nagy

Plant Pathology Faculty Publications

Replication of plus-strand RNA viruses depends on host factors that are recruited into viral replicase complexes. Previous studies showed that eukaryotic translation elongation factor (eEF1A) is one of the resident host proteins in the highly purified tombusvirus replicase complex. Using a random library of eEF1A mutants, we identified one mutant that decreased and three mutants that increased Tomato bushy stunt virus (TBSV) replication in a yeast model host. Additional in vitro assays with whole cell extracts prepared from yeast strains expressing the eEF1A mutants demonstrated several functions for eEF1A in TBSV replication: facilitating the recruitment of the viral RNA template …

Endothelial Cell Capture Of Heparin-Binding Growth Factors Under Flow, Bing Zhao, Changjiang Zhang, Kimberly Forsten-Williams, Jun Zhang, Michael Fannon

Ophthalmology and Visual Science Faculty Publications

Circulation is an important delivery method for both natural and synthetic molecules, but microenvironment interactions, regulated by endothelial cells and critical to the molecule's fate, are difficult to interpret using traditional approaches. In this work, we analyzed and predicted growth factor capture under flow using computer modeling and a three-dimensional experimental approach that includes pertinent circulation characteristics such as pulsatile flow, competing binding interactions, and limited bioavailability. An understanding of the controlling features of this process was desired. The experimental module consisted of a bioreactor with synthetic endothelial-lined hollow fibers under flow. The physical design of the system was incorporated …

Retention And Loss Of Rna Interference Pathways In Trypanosomatid Protozoans, Lon-Fye Lye, Katherine Owens, Huafang Shi, Silvane M. F. Murta, Ana Carolina Vieira, Salvatore J. Turco, Christian Tschudi, Elisabetta Ullu, Stephen M. Beverley

Molecular and Cellular Biochemistry Faculty Publications

RNA interference (RNAi) pathways are widespread in metaozoans but the genes required show variable occurrence or activity in eukaryotic microbes, including many pathogens. While some Leishmania lack RNAi activity and Argonaute or Dicer genes, we show that Leishmania braziliensis and other species within the Leishmania subgenus Viannia elaborate active RNAi machinery. Strong attenuation of expression from a variety of reporter and endogenous genes was seen. As expected, RNAi knockdowns of the sole Argonaute gene implicated this protein in RNAi. The potential for functional genetics was established by testing RNAi knockdown lines lacking the paraflagellar rod, a key component of the …

The Combined Effect Of Environmental And Host Factors On The Emergence Of Viral Rna Recombinants, Hannah M. Jaag, Peter D. Nagy

Plant Pathology Faculty Publications

Viruses are masters of evolution due to high frequency mutations and genetic recombination. In spite of the significance of viral RNA recombination that promotes the emergence of drug-resistant virus strains, the role of host and environmental factors in RNA recombination is poorly understood. Here we report that the host Met22p/Hal2p bisphosphate-3'-nucleotidase regulates the frequency of viral RNA recombination and the efficiency of viral replication. Based on Tomato bushy stunt virus (TBSV) and yeast as a model host, we demonstrate that deletion of MET22 in yeast or knockdown of AHL, SAL1 and FRY1 nucleotidases/phosphatases in plants leads to increased TBSV recombination …

Plant Phenolics: Extraction, Analysis And Their Antioxidant And Anticancer Properties, Jin Dai, Russell J. Mumper

Pharmaceutical Sciences Faculty Publications

Phenolics are broadly distributed in the plant kingdom and are the most abundant secondary metabolites of plants. Plant polyphenols have drawn increasing attention due to their potent antioxidant properties and their marked effects in the prevention of various oxidative stress associated diseases such as cancer. In the last few years, the identification and development of phenolic compounds or extracts from different plants has become a major area of health- and medical-related research. This review provides an updated and comprehensive overview on phenolic extraction, purification, analysis and quantification as well as their antioxidant properties. Furthermore, the anticancer effects of phenolics in-vitro …

Agmatine And Agmatine Analogs In The Treatment Of Epilepsy, Seizure, And Electroconvulsive Disorders, Peter A. Crooks, Aimee K. Bence, David R. Worthen

Pharmaceutical Sciences Faculty Patents

Pharmaceutical preparations containing of agmatine, congeners, analogs or derivatives thereof for use in preventing or treating epilepsy, seizures and other electroconvulsive disorders are provided. Embodiments include administering an effective amount of agmatine, an agmatine analog or a pharmaceutically acceptable salt thereof to a human subject in need of treatment or prevention of epilepsy, seizure or other electroconvulsive disorder to treat, reduce, or prevent the disorder in the subject.

Composition And Methods For Treating Yersinia Pestis Infection, Susan C. Straley, Brian S. Murphy, Stanislav Forman, Christine R. Wulff, Robert D. Perry, Tanya Myers-Morales

Microbiology, Immunology and Molecular Genetics Faculty Patents

Compositions and methods for treating a Yersinia pestis (Y. pestis) infection are provided. Compositions and methods of for inducing an immune response in a subject are provided. Composition can include a YadC polypeptide.

The Us Preventive Service Taskforce And The Guide To Clinical Preventive Services., F. Douglas Scutchfield Md

Preventive Medicine and Environmental Health Presentations

No abstract provided.

Global Ky (Fall 2010), University Of Kentucky International Center

Global Kentucky

No abstract provided.

Educational Innovations: Categories Of Bulletin Board Postings Designed To Increase Awareness Of Contemporary Pharmaceutical Policy Issues, Jacob T. Painter, Joseph L. Fink Iii

Pharmacy Practice and Science Faculty Publications

OBJECTIVE: The goal of this project was to categorize and classify bulletin board postings pertaining to pharmaceutical policy from both the professional and lay press.

METHODS: Bulletin board postings were used to supplement in-class discussion to keep students, faculty and staff up-to-date on emerging trends. A bulletin board located in the main classroom area of the College of Pharmacy Building where students would pass by on the way to class and congregate during break periods was used to display articles from various sources concerning topics related to pharmaceutical policy. Information is presented about the primary subject matters addressed …

Service Technician Working Alone Dies After Being Assaulted, Kentucky Injury Prevention And Research Center

Fatality Case Reports--Other

One late fall evening in 2009, a 53 year-old male technician was working alone at a repair shop. At approximately 9:45 PM, the technician returned to the shop with his dinner from a nearby fast-food establishment. He spread his dinner on the work bench and began eating when apparently he was attacked from behind. His attacker used a knife and cut the technician’s carotid artery and jugular vein on the left side of his neck. The attacker fled, and the technician used a cell phone to call 911, emergency medical services (EMS). When EMS arrived, they found the technician dead …

Brief Of Amicus Curiae Id Software Llc In Support Of Respondents, Paul E. Salamanca, James T. Drakeley, D. Wade Cloud Jr., Kevin J. Keith, J. Griffin Lesher, Amy Yeung

Law Faculty Advocacy

No abstract provided.

Hepatitis C Virus Core-Derived Peptides Inhibit Genotype 1b Viral Genome Replication Via Interaction With Ddx3x, Chaomin Sun, Cara T. Pager, Guangxiang Luo, Peter Sarnow, Jamie H. D. Cate

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The protein DDX3X is a DEAD-box RNA helicase that is essential for the hepatitis C virus (HCV) life cycle. The HCV core protein has been shown to bind to DDX3X both in vitro and in vivo. However, the specific interactions between these two proteins and the functional importance of these interactions for the HCV viral life cycle remain unclear. We show that amino acids 16-36 near the N-terminus of the HCV core protein interact specifically with DDX3X both in vitro and in vivo. Replication of HCV replicon NNeo/C-5B RNA (genotype 1b) is significantly suppressed in HuH-7-derived cells expressing green fluorescent …

Sialic Acid Transport And Catabolism Are Cooperatively Regulated By Siar And Crp In Nontypeable Haemophilus Influenzae, Jason W. Johnston, Haider Shamsulddin, Anne-Frances Miller, Michael A. Apicella

Microbiology, Immunology, and Molecular Genetics Faculty Publications

BACKGROUND: The transport and catabolism of sialic acid, a critical virulence factor for nontypeable Haemophilus influenzae, is regulated by two transcription factors, SiaR and CRP.

RESULTS: Using a mutagenesis approach, glucosamine-6-phosphate (GlcN-6P) was identified as a co-activator for SiaR. Evidence for the cooperative regulation of both the sialic acid catabolic and transport operons suggested that cooperativity between SiaR and CRP is required for regulation. cAMP was unable to influence the expression of the catabolic operon in the absence of SiaR but was able to induce catabolic operon expression when both SiaR and GlcN-6P were present. Alteration of helical phasing supported …

Hiv-1 Reactivation Induced By The Periodontal Pathogens Fusobacterium Nucleatum And Porphyromonas Gingivalis Involves Toll-Like Receptor 2 And 9 Activation In Monocytes/Macrophages, Octavio A. Gonzalez, Mengtao Li, Jeffrey L. Ebersole, Chifu B. Huang

Center for Oral Health Research Faculty Publications

Although oral coinfections (e.g., periodontal disease) are highly prevalent in human immunodeficiency virus type 1-positive (HIV-1⁺) patients and appear to positively correlate with viral load levels, the potential for oral bacteria to induce HIV-1 reactivation in latently infected cells has received little attention. We showed that HIV-1 long terminal repeat (LTR) promoter activation can be induced by periodontopathogens in monocytes/macrophages; nevertheless, the mechanisms involved in this response remain undetermined. Since Toll-like receptor 2 (TLR2), TLR4, and TLR9 activation have been involved in HIV-1 recrudescence, we sought to determine the role of these TLRs in HIV-1 reactivation induced by …

Association Between Chronic Liver And Colon Inflammation During The Development Of Murine Syngeneic Graft-Versus-Host Disease, Jason Anthony Brandon, Jacqueline Perez-Rodriguez, C. Darrell Jennings, Donald A. Cohen, Vishal J. Sindhava, Subbarao Bondada, Alan M. Kaplan, J. Scott Bryson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The murine model of cyclosporine A (CsA)-induced syngeneic graft-versus-host disease (SGVHD) is a bone marrow (BM) transplantation model that develops chronic colon inflammation identical to other murine models of CD4⁺ T cell-mediated colitis. Interestingly, SGVHD animals develop chronic liver lesions that are similar to the early peribiliary inflammatory stages of clinical chronic liver disease, which is frequently associated with inflammatory bowel disease (IBD). Therefore, studies were initiated to investigate the chronic liver inflammation that develops in the SGVHD model. To induce SGVHD, mice were lethally irradiated, reconstituted with syngeneic BM, and treated with CsA. All of the SGVHD animals …

Identification Of A Unique Core Domain Of Par-4 Sufficient For Selective Apoptosis Induction In Cancer Cells, Vivek M. Rangnekar

Radiation Medicine Faculty Patents

The present invention relates to Par-4 mutants which cause apoptosis in cancer cells which are sensitive to Par-4 and also induce apoptosis in cancer cells which are resistant to Par-4. The present invention also relates to methods of using the Par-4 mutant to treat certain cancers, as well as to kits, vectors, and polypeptides for same.

Inhibition Of Allogeneic Inflammatory Responses By The Ribonucleotide Reductase Inhibitors, Didox And Trimidox, Mohammed S. Inayat, Ismail S. El-Amouri, Mohammad Bani-Ahmad, Howard L. Elford, Vincent S. Gallicchio, Oliver R. Oakley

Health and Clinical Sciences Faculty Publications

BACKGROUND: Graft-versus-host disease is the single most important obstacle facing successful allogeneic stem cell transplantation (SCT). Even with current immunosuppressive therapies, morbidity and mortality rates are high. Current therapies including cyclosporine A (CyA) and related compounds target IL-2 signaling. However, although these compounds offer great benefit, they are also associated with multiple toxicities. Therefore, new compounds with a greater efficacy and reduced toxicity are needed to enable us to overcome this hurdle.

METHODS: The allogeneic mixed lymphocyte reaction (MLR) is a unique ex vivo method to study a drug's action on the initial events resulting in T-cell activation and proliferation, …

Foreign-Born Semi Driver Dies After Driving Over Embankment, Kentucky Injury Prevention And Research Center

Fatality Case Reports--Motor Vehicle

One summer morning in 2009, at approximately 11:30 AM, a 41 year-old male, long-haul, semi tractor-trailer driver drove off an interstate highway, over a guardrail, and continued into a wooded ravine. His trailer was empty and he was travelling to pick up a load of retail goods. The trailer disengaged from the tractor, the fuel tanks ruptured, the tractor overturned and caught fire. As the tractor overturned, the driver was ejected. A passing motorist called emergency medical (EMS) services; EMS arrived and found the driver dead at the scene.

To prevent future occurrences of similar incidents, the following recommendations have …

2010 Driver Attitudes And Awareness Survey, Kenneth R. Agent, Eric R. Green, Ronald E. Langley

Kentucky Transportation Center Research Report

A basic set of questions were developed that could be used in periodic surveys that track drivers attitudes and awareness concerning impaired driving, seat belt use, and speeding issues. The objective of the survey was to learn the knowledge, views, and behaviors of drivers in these areas. The objective of this report is to document the results of the 2010 baseline survey.

The method used to conduct the survey was a telephone survey. In addition to questions for the three major highway safety areas of impaired driving, seat belt use, and speeding, an additional question was added which dealt with …

Bioactive Peptide-Based Probes, Clair D. Hicks, Peter A. Crooks

Pharmaceutical Sciences Faculty Patents

A method for preparing a site-specific peptide probe, wherein the peptide is specific to a receptor, includes modifying a marker to include a tether molecule and covalently binding the tether molecule to the peptide. The present invention also provides a labeled probe, comprising a peptide specific for a receptor and a marker. The marker is modified to include a tether molecule capable of covalently binding to the peptide. The peptide is typically derived from a bacteriophage or is a synthetic analog or derivative of the peptide. The receptor will typically be found on a surface of a bacterial cell. The …

Interleukin-10 Mediated Autoregulation Of Murine B-1 B-Cells And Its Role In Borrelia Hermsii Infection, Vishal Sindhava, Michael E Woodman, Brian Stevenson, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

B cells are typically characterized as positive regulators of the immune response, primarily by producing antibodies. However, recent studies indicate that various subsets of B cells can perform regulatory functions mainly through IL-10 secretion. Here we discovered that peritoneal B-1 (B-1P) cells produce high levels of IL-10 upon stimulation with several Toll-like receptor (TLR) ligands. High levels of IL-10 suppressed B-1P cell proliferation and differentiation response to all TLR ligands studied in an autocrine manner in vitro and in vivo. IL-10 that accumulated in cultures inhibited B-1P cells at second and subsequent cell divisions mainly at the G1/S interphase. …

Talmidae Rhetoricae: Drashing Up Models And Methods For Jewish Rhetorical Studies, Janice W. Fernheimer

Writing, Rhetoric, and Digital Studies Faculty Publications

No abstract provided.

Southeastern Law Librarian Summer 2010, Seaall

Newsletters

No abstract provided.

The Role Of Trust Protectors In American Trust Law, Richard C. Ausness

Law Faculty Scholarly Articles

“A trust is an arrangement whereby one person (the trustor) transfers property to another person or entity (the trustee) and directs the trustee to hold the property for the benefit of another person (the beneficiary).” These days, trustees often have significant discretionary and administrative powers. The increased use of institutional trustees, as well as the growing sophistication and complexity of modern trust asset management, have induced many settlors to give their trustees greater power and discretion. In addition, many states have enacted statutes, such as the Uniform Trustees’ Powers Act or the Uniform Trust Code (UTC), that confer broad powers …