Microbiology Commons^™

Design, Synthesis, And Evaluation Of 10-N-Substituted Acridones As Novel Chemosensitizers In Plasmodium Falciparum, Jane X. Kelly, Martin J. Smilkstein, Roland A. Cooper, Kristin D. Lane, Robert A. Johnson, Aaron Janowsky, Rozalia A. Dodean, David J. Hinrichs, Rolf Winter, Michael Riscoe

Biological Sciences Faculty Publications

A series of novel 10-N-substituted acridones, bearing alkyl side chains with tertiary amine groups at the terminal position, were designed, synthesized, and evaluated for the ability to enhance the potency of quinoline drugs against multidrug-resistant (MDR) Plasmodium falciparum malaria parasites. A number of acridone derivatives, with side chains bridged three or more carbon atoms apart between the ring nitrogen and terminal nitrogen, demonstrated chloroquine (CQ)-chemosensitizing activity against the MDR strain of P. falciparum (Dd2). Isobolograrn analysis revealed that selected candidates demonstrated significant synergy with CQ in the CQ-resistant (CQR) parasite Dd2 but only additive (or indifferent) interaction in the CQ-sensitive …

Hypoxic Induction And The Role Of Hifs In The Activation Of Luciferase Constitutive Reporters In Placental Stem Cells, Diane Michelle Doran

Browse all Theses and Dissertations

Hypoxia is critically important to the development of the embryo and placenta. Proper placental development is critical for normal fetal growth and embryonic survival. Abnormal placental development has been implicated in numerous obstetric complications, including preeclampsia, which affects about 7% of all pregnancies and can be fatal for both mother and baby. Rodent and murine trophoblast stem cells differentiate into three distinct cell lineages: giant cells, spongiotrophoblasts, and labyrinthine cells, which form different layers and have different functions within the placenta. Recent studies in our laboratory have focused on the invasive giant cell layer using the rodent Rcho-1 choriocarcinoma stem …

On A Multinational Assessment Of Rotavirus Disease In Europe, David O. Matson

Community & Environmental Health Faculty Publications

Rotaviruses were discovered in the 1960s in animals and in the 1970s in humans; the latter discovery was made by an intrepid group who performed duodenal biopsies on children with acute gastroenteritis (AGE) [1]. By the late 1970s, data already clearly indicated that rotavirus was the cause of the annual winter peak of AGE affecting young children, as well as a frequent cause of severe gastroenteritis in various animal species (e.g., [2–5]). Use of the retrospectroscope clarified or left as tantalizing the suggestion that rotaviruses were the cause of the annual “winter vomiting syndrome” first described in children in 1910 …

Potential For Stimulating Host Anti-Tumor Immune Response Via Rnai-Mediated Local Foxp3 Knockdown, N. Klaiber

Chemistry & Biochemistry Faculty Publications

Neoplastic growths represent a unique challenge for the host immune system. As they are indeed derived from self, many of the same mechanisms operating to prevent autoimmunity also provide an umbrella beneath which malignant cells are free to proliferate.1 Central among these immune regulatory boundaries are an influential subset of lymphocytes known as T regs. Hypothesized to exist decades ago, yet eluding definitive characterization until relatively recently, T regs have been demonstrated to play a crucial role in the proper functioning of the immune system as a whole. They may also, however, represent one of the primary obstacles to successful …

Mutations In Transmembrane Domains 1, 4 And 9 Of The Plasmodium Falciparum Chloroquine Resistance Transporter Alter Susceptibility To Chloroquine, Quinine And Quinidine, Roland A. Cooper, Kristan D. Lane, Bingbing Deng, Jianbing Mu, Jigar J. Patel, Thomas E. Wellems, Xinzhuan Su, Michael T. Ferdig

Biological Sciences Faculty Publications

Mutations in the Plasmodium falciparum chloroquine (CQ) resistance transporter (PfCRT) can result in verapamil-reversible CQ resistance and altered susceptibility to other antimalarials. PfCRT contains 10 membrane-spanning domains and is found in the digestive vacuole (DV) membrane of intraerythrocytic parasites. The mechanism by which PfCRT mediates CQ resistance is unclear although it is associated with decreased accumulation of drug within the DV. On the permissive background of the P. falciparum 106/1(K76) parasite line, we used single-step drug selection to generate isogenic clones containing unique pfcrt point mutations that resulted in amino acid changes in PfCRT transmembrane domains 1 (C72R, K76N, K76I …

Design Of A Bioreactor To Study The Role Of Red Blood Cells In The Transport Of Nitric Oxide In The Microcirculation, Nupura Bhise, Mahendra Kavdia

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

Nitric oxide (NO) plays an important role in physiological functions like vasodilation, neurotransmission, and inhibition of platelet aggregation. The endothelium-derived NO diffuses into the vascular lumen where it interacts with flowing blood as well as the smooth muscles where it modulates vascular tone. However, uncertainty exists on how NO escapes the rapid scavenging by hemoglobin (Hb) and reaches smooth muscles. Several proposed hypotheses include 1) a reduced reaction rate of NO with Hb contained inside red blood cells (RBCs) and 2) NO preservation in the bound form of s-nitrosohemoglobin or nitrite. The mechanism and magnitude of reduction of NO reaction …

Assessment Of Key Parameters To Achieve Bacteria Transformability In E. Coli And A. Tumefaciens, Zach Regelin

Honors Program Theses

ln this project, growth and transformability of E. coli and A. tumefaciens were investigated. The growth of the bacterial species was monitored under different key parameters including: the strain of the bacteria, the inoculum source (a fresh plate or frozen glycerol stock), and the media type. Growth was monitored by measuring the optical density (OD). Using E. coli strains Dh5a and CdB\ it was determined that the strain, the media type, and the amount of inoculum had a great effect on the growth but the source of the inoculum had little effect. For A. tumefaciens, the strain and the media …

Microbiological Enhancement Of Phosphorus Sequestration In Iron-Enriched Sediments, Lindsay Marie Sandersfeld

Honors Program Theses

An overabundance of phosphorus, primarily due to agricultural run off, is the source of increases in unwanted algae in Iowa's surface waters. Oxidized iron found in mine tailings will sequester phosphorus in sediments and prevent it from entering surface waters. Therefore, adding mine tailings to wetlands is a cheap and easy way to eliminate phosphorus pollution. This phosphorus removal process is enhanced by a microbial component that biochemically solubilizes iron tailings which allows them to efficiently react with free phosphorus in the water. The purpose of this project was to characterize the microbial component in this process. Ferric citrate medium …

Humboldt Journal Of Microbiology: Volume 9, Number 1- May 2007, Press Humboldt

Humboldt Journal of Microbiology

No abstract provided.

Comparative Predictive Value Of Three Prognostic Markers--S-Phase Fraction, Pcna And Mitotic Count On Axillary Lymph Node Metastasis In Carcinoma Breast, Shahid Pervez, Muhammad Nadeem Khan, Muhammad Israr Nasir

Department of Pathology and Laboratory Medicine

Background: Axillary lymph node metastasis is the single most important prognostic factor in carcinoma of the breast. Therefore, prognostic markers that may reliably predict probability of lymph node (LN) metastases are of great value. This study was conducted to compare the predictive value of two novel prognostic / proliferative markers i.e. S-phase fraction (SPF) and proliferating cell nuclear antigen (PCNA) in parallel with mitotic index.

Methods: Data of consecutive cases of infiltrating ductal carcinoma (IDC) breast diagnosed from July 2003 to July 2004 at the section of the Histopathology, The Aga Khan University Hospital, Karachi, were reviewed. A total of …

Comparison Study Of The Averaged Sediment Microbial Enzyme Activities In Four Fecally-Contaminated Streams In The Same Watershed In Northeast Tennessee To Biochemical Oxygen Demand, Nitrate Concentration, And Phosphate Concentration, Brian G. Evanshen, Kurt J. Maier, Phillip R. Scheuerman

ETSU Faculty Works

Microbial enzyme activities (MEA’s) are measurements of microbial metabolism. These activities are dependent on the need for nutrients and respiration. This extended study evaluated four streams in the same watershed that had an approved fecal coliform Total Maximum Daily Load. Sediment and water samples were collected monthly for the first year of each specific stream study, and then quarterly to the end of 2006. Dehydrogenase, a measure of microbial respiration, along with acid phosphatase, alkaline phosphatase, galactosidase and glucosidase activities were measured using colorimetric assays. Biochemical oxygen demand (BOD) was determined using the standard 5-day test (BOD₅). Nitrate …

Evaluation Of Four Novel Broad-Host-Range Antimicrobial Agents., Jiahui Guo

Theses

The overall objective of this thesis was to evaluate the antimicrobial effects of four novel broad-host-range antimicrobial agents. The first was a milk-derived lipoprotein developed by Westgate Biologicals with the support of Enterprise Ireland. This lipoprotein which was designated LactiSAL, was evaluated against a wide range of bacterial species associated with humans. Essentially, the LactiSAL was incorporated at a variety of concentrations into agar media, which were appropriate for cultivation of the different genera. Agars were examined for colony formation, after which it was possible to quantify the minimal inhibitory concentration for each genus. Subsequently, LactiSAL was incorporated at levels …

Chemical Defenses: From Compounds To Communities, Valerie J. Paul, Koty H. Sharp

Arts & Sciences Faculty Publications

Marine natural products play critical roles in the chemical defense of many marine organisms and in some cases can influence the community structure of entire ecosystems. Although many marine natural products have been studied for biomedical activity, yielding important information about their biochemical effects and mechanisms of action, much less is known about ecological functions. The way in which marine consumers perceive chemical defenses can influence their health and survival and determine whether some natural products persist through a food chain. This article focuses on selected marine natural products, including okadaic acid, brevetoxins, lyngbyatoxin A, caulerpenyne, bryostatins, and isocyano terpenes, …

Characteristics Of A Foamy Virus-Derived Vector That Allow For Safe Autologous Gene Therapy To Correct Leukocyte Adhesion Deficiency Type 1, Ryan Matthew Mcnichol

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The hematopoeitic stem cell is a prime target for gene therapy in the attempt to correct a number of single gene inherited genetic defects that affect the immune system. In persons affected by leukocyte adhesion deficiency type 1 (LAD-1) the gene for the Beta-2 subunit of the integrin molecule is mutated. This autosomal recessive gene defect yields a phenotype with little or no beta-2 integrin expression on leukocytes. Beta-2 integrin expression is essential for leukocytes to travel from the blood to the tissues to fight infection. Persons with this disease have lowered leukocyte counts in the tissues and as a …

Hsv-1 Infection Of C3h Central Nervous System Cell Lines, Lauren Kay Van Buren

Browse all Theses and Dissertations

Herpes Simplex Virus Type 1 (HSV-1) can infect the nervous system, resulting in a disease known as herpes encephalitis (HSE). Herpes encephalitis affects thousands of people each year; many cases are fatal or permanently debilitating. Approximately two thousand known cases occur in the United States each year alone (Neuroland online source). Acyclovir has been the drug of choice used to treat herpes encephalitis. Even after the administration of acyclovir, permanent neurological damage and/or death often results. Thousands of individuals would benefit by the discovery of drugs that are more effective at preventing lasting HSE damage and death. Knowledge concerning HSE …

Discovery Of New Antimicrobial Agents Using Combinatorial Chemistry, William I. Northern

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Combinatorial chemistry has become an important aspect of medicinal research due to its flexibility and the ability to produce large numbers of potential therapeutic agents. Once compounds are made, they must be screened to determine if there is any biological activity. This research project focused on developing a screening method for chemical agents produced by a graduate student in the chemistry department at Wright State University. After an acceptable screening method was found, the goal of the project was to determine if compounds produced had either antibacterial activity, antifungal activity, or both. Seven compounds exhibited biological activity. Two of these …

Structural Definition Of A Conserved Neutralization Epitope On Hiv-1 Gp120, Tongqing Zhou, Ling Xu, Barna Dey, Ann J. Hessell, Donald Van Ryk, Shi-Hua Xiang, Xinzhen Yang, Mei-Yun Zhang, Michael B. Zwick, James Arthos, Dennis R. Burton, Dimiter S. Dimitrov, Joseph Sodroski, Richard Wyatt, Gary J. Nabel, Peter D. Kwong

Nebraska Center for Virology: Faculty Publications

The remarkable diversity, glycosylation and conformational flexibility of the human immunodeficiency virus type 1 (HIV-1) envelope (Env), including substantial rearrangement of the gp120 glycoprotein upon binding the CD4 receptor, allow it to evade antibody-mediated neutralization. Despite this complexity, the HIV-1 Env must retain conserved determinants that mediate CD4 binding. To evaluate how these determinants might provide opportunities for antibody recognition, we created variants of gp120 stabilized in the CD4-bound state, assessed binding of CD4 and of receptor-binding-site antibodies, and determined the structure at 2.3Å resolution of the broadly neutralizing antibody b12 in complex with gp120. b12 binds to a conformationally …

Structures Of The Ccr5 N Terminus And Of A Tyrosine-Sulfated Antibody With Hiv-1 Gp120 And Cd4, Chih-Chin Huang, Son N. Lam, Priyamvada Acharya, Min Tang, Shi-Hua Xiang, Syed Shahzad-Ul Hussan, Robyn L. Stanfield, James Robinson, Ian A. Wilson, Richard Wyatt, Carole A. Bewley, Peter D. Kwong

Nebraska Center for Virology: Faculty Publications

The CCR5 co-receptor binds to the HIV-l gp120 envelope glycoprotein and facilitates HIV-l entry into cells. Its N terminus is tyrosine-sulfated, as are many antibodies that react with the co-receptor binding site on gp120. We applied nuclear magnetic resonance and crystallographic techniques to analyze the structure of the CCR5 N terminus and that of the tyrosine-sulfated antibody 412d in complex with gp120 and CD4. The conformations of tyrosine-sulfated regions of CCR5 (α-helix) and 412d (extendedloop) are surprisingly different. Nonetheless, a critical sulfotyrosine on CCR5 and on 412d induces similar structural rearrangements in gp120. These results now provide a framework for …

Functional Interplay Between The B-Box 2 And The B30.2(Spry) Domains Of Trim5Α, Xi Ling, Byeongwoon Song, Shi-Hua Xiang, Joseph Sodroski

Nebraska Center for Virology: Faculty Publications

The retroviral restriction factors, TRIM5α and TRIMCyp, consist of RING and B-box 2 domains separated by a coiled coil from carboxy-terminal domains. These carboxy-terminal domains (the B30.2(SPRY) domain in TRIM5α and the cyclophilin A domain in TRIMCyp) recognize the retroviral capsid. Here we show that some B-box 2 changes in TRIM5α, but not in TRIMCyp, resulted in decreased human immunodeficiency virus (HIV-1) capsid binding. The phenotypic effects of these B-box 2 changes on the restriction of retroviral infection depended on the potency of restriction and the affinity of the TRIM5α interaction with the viral capsid, two properties specified by the …

Characterization Of Human Immunodeficiency Virus Type 1 Monomeric And Trimeric Gp120 Glycoproteins Stabilized In The Cd4-Bound State: Antigenicity, Biophysics, And Immunogenicity, Barna Dey, Marie Pancera, Krisha Svehla, Yuuei Shu, Shi-Hua Xiang, Jeffrey Vainshtein, Yuxing Li, Joseph Sodroski, Peter D. Kwong, John R. Mascola, Richard Wyatt

Nebraska Center for Virology: Faculty Publications

The human immunodeficiency virus type 1 exterior gp120 envelope glycoprotein is highly flexible, and this flexibility may contribute to the inability of monomeric gp120 immunogens to elicit broadly neutralizing antibodies. We previously showed that an S375W modification of a critical interfacial cavity central to the primary receptor binding site, the Phe43 cavity, stabilizes gp120 into the CD4-bound state. However, the immunological effects of this cavity-altering replacement were never tested. Subsequently, we screened other mutations that, along with the S375W alteration, might further stabilize the CD4-bound state. Here, we define a selected second cavity-altering replacement, T257S, and analyze the double mutations …

Georgeoral Immunization Of Rhesus Macaques With Adenoviral Hiv Vaccines Using Enteric-Coated Capsules, George T. Mercier, Pramod N. Nehete, Marco F. Passeri, Bharti N. Nehete, Eric A. Weaver, Nancy Smyth Templeton, Kimberly Schluns, Stephanie S. Buchl, K. Jagannadha Sastry, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Targeted delivery of vaccine candidates to the gastrointestinal (GI) tract holds potential for mucosal immunization, particularly against mucosal pathogens like the human immunodeficiency virus (HIV). Among the different strategies for achieving targeted release in the GI tract, namely the small intestine, pH sensitive enteric coating polymers have been shown to protect solid oral dosage forms from the harsh digestive environment of the stomach and dissolve relatively rapidly in the small intestine by taking advantage of the luminal pH gradient. We developed an enteric polymethacrylate formulation for coating hydroxy-propyl-methyl-cellulose (HPMC) capsules containing lyophilized Adenoviral type 5 (Ad5) vectors expressing HIV-1 gag …

A Protein Encoded By The Bovine Herpesvirus 1 Latency-Related Gene Interacts With Specific Cellular Regulatory Proteins, Including Ccaat Enhancer Binding Protein Alpha, Florencia Meyer, Sandra Perez, Vicki Geiser, Mark Sintek, Melissa Inman, Clinton J. Jones

Nebraska Center for Virology: Faculty Publications

Following acute infection, bovine herpesvirus 1 establishes latency in sensory neurons of trigeminal ganglia (TG). Reactivation from latency occurs periodically, resulting in the shedding of infectious virus. The latency-related (LR) RNA is abundantly expressed in TG of latently infected calves, and the expression of LR proteins is necessary for dexamethasone-induced reactivation from latency. Previously published studies also identified an alternatively spliced LR transcript which is abundantly expressed in TG at 7 days after infection and has the potential to encode a novel LR fusion protein. Seven days after infection is when extensive viral gene expression is extinguished in TG and …

Genetic Microheterogeneity And Phenotypic Variation Of Helicobacter Pylori Arginase In Clinical Isolates, Justin Hovey, Emily Watson, Melanie Langford, Ellen Hildebrandt, Sangeetha Bathala, Jeffrey Bolland, Domenico Spadafora, George Mendz, David Mcgee

School of Biological Sciences: Faculty Publications

Background: Clinical isolates of the gastric pathogen Helicobacter pylori display a high level of genetic macro- and microheterogeneity, featuring a panmictic, rather than clonal structure. The ability of H. pylori to survive the stomach acid is due, in part, to the arginase-urease enzyme system. Arginase (RocF) hydrolyzes L-arginine to L-ornithine and urea, and urease hydrolyzes urea to carbon dioxide and ammonium, which can neutralize acid.

Results: The degree of variation in arginase was explored at the DNA sequence, enzyme activity and protein expression levels. To this end, arginase activity was measured from 73 minimally-passaged clinical isolates and six laboratory-adapted strains …

Evolutionary Endocrinology: The Developing Synthesis Between Endocrinology And Evolutionary Genetics, Anthony J. Zera, Lawrence G. Harshman, Tony D. Williams

Anthony Zera Publications

A productive synthesis of endocrinology and evolutionary genetics has occurred during the past two decades, resulting in the first direct documentation of genetic variation and correlation for endocrine regulators in nondomesticated animals. In a number of insect genetic polymorphisms (dispersal polymorphism in crickets, butterfly wing-pattern polymorphism), blood levels of ecdysteroids and juvenile hormone covary with morphology, development, and life history. Genetic variation in insulin signaling may underlie life history trade-offs in Drosophila. Vertebrate studies identified variation in brain neurohormones, bone-regulating hormones, and hormone receptor gene sequences that underlie ecologically important genetic polymorphisms. Most work to date has focused on genetically …

Sensory Genes And Mate Choice: Evidence That Duplications, Mutations, And Adaptive Evolution Alter Variation In Mating Cue Genes And Their Receptors, Lisa Horth

Biological Sciences Faculty Publications

Fascinating new data, revealed through gene sequencing, comparative genomics, and genetic engineering, precisely establish which genes are involved in mate choice and mating activity—behaviors that are surprisingly understudied from a genetic perspective. Discussed here are some of the recently identified visual and chemosensory genes that are involved in mate choice and mating behavior. These genes’ products are involved in the production, transmission, and receipt of crucial sensory mate-choice cues that affect fitness. This review exposes newfound evidence that alternative splicing, gene-expression pattern changes, and molecular genetic variation in sensory genes are crucial for both intra- and interspecific mate choice and …

Establishment And Maintenance Of An Asm Student Chapter, Amy Cheng Vollmer

Biology Faculty Works

No abstract provided.

Characterization Of Mycobacterium Tuberculosis Central Asian Strain 1 Using Mycobacterial Interspersed Repetitive Unit Genotyping, Asho Ali, Zahra Hasan, Mahnaz Tanveer, Amna Siddiqui, Solomon Ghebremichael, Gunilla Kallenius, Rumina Hasan

Department of Pathology and Laboratory Medicine

Background:
The Central Asian Strain1 (CAS1) genogroup of Mycobacterium tuberculosis (MTB) is the most prevalent in Pakistan, India and Bangladesh. Mycobacterial interspersed repetitive units variable number tandem repeat (MIRU-VNTR) typing is a reliable and reproducible method for differentiation of MTB isolates. However, information of its utility in determining the diversity of CAS1 strain is limited. We performed standard 12 loci based MIRU-VNTR typing on previously spoligotyped CAS1 strains and 'unique' strains in order to evaluate its discriminatory power for these isolates.
Methods:
Twelve loci based MIRU- VNTR typing was used to type178 CAS1 and 189 'unique' MTB strains. The discriminatory …

Extending And Measuring The Quality Of Fresh-Cut Fruit And Vegetables: A Review, Ana Belen Martin-Diana, Daniel Rico, Gary Henehan, Jesus Maria Frias, J. Barat

Articles

The market sales of ready - to - use vegetables have grown rapidly in recent decades as a result of changes in consumer attitudes especially consumption of fresh-cut lettuce and carrot due to their use in prepared salads. Chlorine solutions have been widely used to sanitise fruit and vegetables in the fresh-cut industry. However, the association of chlorine with the possible formation of carcinogenic chlorinated compounds in water has called into question the use of chlorine in food processing. There is a real need to find alternatives for preservation of fresh-cut fruit and vegetables in order to improve the efficacy …

Good Things Come In Small Packages: Tiny Plankton Producing Oxygen Near Dead Zone, Abbie Basile

Libraries Faculty & Staff Publications

(First paragraph) For many, the words “Lake Erie” bring to mind large things: big sport fish, sprawling waterfront homes, and an enormous body of water bordering four states and two countries. Similarly, much of the Lake Erie research of which the public is aware deals with larger biological organisms—larger algae and zooplankton, the small fish that eat the zooplankton, and the large fish that feed on those smaller fish. Over the years, the smaller lake life have been somewhat overlooked.

Human Papillomavirus Prevalence And Genotypes In An Opportunistically Screened Irish Female Population, Helen Keegan, Fergus Ryan, Alison Malkin, Mairead Griffin, Helen Lambkin

Articles

This study aims to evaluate human papillomavirus (HPV) prevalence and predominating genotypes in liquid-based cervical cytology samples from an Irish urban female population. In addition to use of routine cervical cytology testing, women are screened for HPV using the MY09/11 primers for the HPV L1 gene and primers for β-globin amplification in a multiplex format. Overall, 996 women between the ages of 16 and 72 years (average age: 35) are included in the study and HPV prevalence was 19.8%. Cytology results showed that 88.9% were normal, 9% borderline or mild dyskaryosis, 1.1% moderate dyskaryosis and 0.9% severe dyskaryosis. Human papillomavirus …