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2006

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Full-Text Articles in Chemicals and Drugs

Functional Association Between Three Archaeal Aminoacyl-Trna Synthetases, Mette Praetorius-Ibba, Corinne D. Hausmann, Molly Paras, Theresa E. Rogers, Michael Ibba Dec 2006

Functional Association Between Three Archaeal Aminoacyl-Trna Synthetases, Mette Praetorius-Ibba, Corinne D. Hausmann, Molly Paras, Theresa E. Rogers, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Aminoacyl-tRNA synthetases (aaRSs) are responsible for attaching amino acids to their cognate tRNAs during protein synthesis. In eukaryotes aaRSs are commonly found in multi-enzyme complexes, although the role of these complexes is still not completely clear. Associations between aaRSs have also been reported in archaea, including a complex between prolyl-(ProRS) and leucyl-tRNA synthetases (LeuRS) in Methanothermobacter thermautotrophicus that enhances tRNAPro aminoacylation. Yeast two-hybrid screens suggested that lysyl-tRNA synthetase (LysRS) also associates with LeuRS in M. thermautotrophicus. Co-purification experiments confirmed that LeuRS, LysRS, and ProRS associate in cell-free extracts. LeuRS bound LysRS and ProRS with a comparable KD …


Tyrosine Phosphorylation Of Villin: Effects On Actin Dynamics, Cell Morphology And Cell Migration, Alok Tomar Dec 2006

Tyrosine Phosphorylation Of Villin: Effects On Actin Dynamics, Cell Morphology And Cell Migration, Alok Tomar

Theses and Dissertations (ETD)

Cell migration is a key aspect of many normal and abnormal biological processes, including embryonic development, defense against infections, wound healing, and tumor cell metastasis. In this study we demonstrate that an epithelial cell actin-binding protein, villin, plays a crucial role in the process of cell migration. Overexpression of villin in doxycyline-regulated HeLa Tet-off and MDCK Tet-off cells enhanced cell migration. We further demonstrate that tyrosine phosphorylation of villin by c-src is required for villin-induced cell migration. Previously, we identified four tyrosine phosphorylation sites in the amino-terminal domain of villin. I further identified six new sites in the carboxylterminal region …


Screening Assay For Inhibitors Of Severe Acute Respiratory Syndrome (Sars) Using Seldi-Tof Mass Spectrometry, Khalid M. Elased, Mariana Morris Nov 2006

Screening Assay For Inhibitors Of Severe Acute Respiratory Syndrome (Sars) Using Seldi-Tof Mass Spectrometry, Khalid M. Elased, Mariana Morris

Pharmacology and Toxicology Faculty Publications

Mass spectrometric methods directed to screening libraries of compounds for agents that inhibit entry of Severe Acute Respiratory Syndrome (SARS) coronavirus (CoV) into cells are provided, along with methods for comparatively evaluating inhibitors of the SARS CoV.


Epigenetics And The Estrogen Receptor, Jennifer E. Leader, Chenuang Wang, Vladimir M. Popov, Maofu Fu, Richard G. Pestell Nov 2006

Epigenetics And The Estrogen Receptor, Jennifer E. Leader, Chenuang Wang, Vladimir M. Popov, Maofu Fu, Richard G. Pestell

Department of Cancer Biology Faculty Papers

The position effect variegation in Drosophila and Schizosaccharomyces pombe, and higher-order chromatin structure regulation in yeast, is orchestrated by modifier genes of the Su(var) group, (e.g., histone deacetylases ([HDACs]), protein phosphatases) and enhancer E(Var) group (e.g., ATP [adenosine 5'-triphosphate]-dependent nucleosome remodeling proteins). Higher-order chromatin structure is regulated in part by covalent modification of the N-terminal histone tails of chromatin, and histone tails in turn serve as platforms for recruitment of signaling modules that include nonhistone proteins such as heterochromatin protein (HP1) and NuRD. Because the enzymes governing chromatin structure through covalent modifications of histones (acetylation, methylation, phosphorylation, ubiquitination) can also …


Demographic Change And Response: Social Context And The Practice Of Birth Control In Six Countries, Sangeeta Parashar, Harriet B. Presser, Megan L. Klein Hattori, Sara Raley, Zhihong Sa Sep 2006

Demographic Change And Response: Social Context And The Practice Of Birth Control In Six Countries, Sangeeta Parashar, Harriet B. Presser, Megan L. Klein Hattori, Sara Raley, Zhihong Sa

Department of Sociology Faculty Scholarship and Creative Works

This paper expands on Kingsley Davis’s demographic thesis of change and re- sponse. Specifically, we consider the social context that accounts for the primacy of particular birth control methods that bring about fertility change during specific time periods. We examine the relevance of state policy (including national family planning programs), the international population establishment, the medical profession, organized religion, and women’s groups using case studies from Japan, Russia, Puerto Rico, China, India, and Cameroon. Some of these countries are undergoing the second demographic transition, others the first. Despite variations in context, heavy reliance on sterilization and/or abortion as a means …


Newly Identified Vitamin K-Producing Bacteria Isolated From The Neonatal Faecal Flora, Gordon Cooke, John Behan, Mary Costello Sep 2006

Newly Identified Vitamin K-Producing Bacteria Isolated From The Neonatal Faecal Flora, Gordon Cooke, John Behan, Mary Costello

Articles

Fat-soluble vitamin K is an essential component of the blood clotting process. Menaquinones are the naturally occurring form of vitamin K identified in bacteria. Lipid extracts were made from three bacteria originally isolated from the human neonatal gut and identified as Enterobacter agglomerans, Serratia marcescens and Enterococcus faecium. Following preparative thin layer chromatography (TLC), the lipid extracts were subjected to liquid chromatography-mass spectrometry (LC-MS) analysis. Peak analysis of the LC-MS data showed that the three bacteria produce various forms of menaquinone.


Gene Expression In The Mouse Placenta: Developmental And Stress Responses, Ciprian P. Gheorghe Sep 2006

Gene Expression In The Mouse Placenta: Developmental And Stress Responses, Ciprian P. Gheorghe

Loma Linda University Electronic Theses, Dissertations & Projects

Successful placental development is crucial for optimal growth, maturation, and survival of the embryo/fetus. Placental failure and placental pathology contributes to both morbidity and mortality of the fetus. We sought to understand normal placental development and also placental responses to stress using oligonucleotide microarray technology. To examine genetic aspects of normal placental development, we investigated gene expression patterns in the murine placenta at embryonic day 10.5 (E10.5), E12.5, E15.5, and E17.5. Hypoxia has been identified as a major stressor in placental and fetal development. In order to comprehend more completely hypoxic stress responses we sought to measure gene expression changes …


Cyclin D1 Repression Of Nuclear Respiratory Factor 1 Integrates Nuclear Dna Synthesis And Mitochondrial Function., Chenguang Wang, Zhiping Li, Yinan Lu, Runlei Du, Sanjay Katiyar, Jianguo Yang, Maofu Fu, Jennifer E Leader, Andrew Quong, Phyllis M Novikoff, Richard Pestell Aug 2006

Cyclin D1 Repression Of Nuclear Respiratory Factor 1 Integrates Nuclear Dna Synthesis And Mitochondrial Function., Chenguang Wang, Zhiping Li, Yinan Lu, Runlei Du, Sanjay Katiyar, Jianguo Yang, Maofu Fu, Jennifer E Leader, Andrew Quong, Phyllis M Novikoff, Richard Pestell

Department of Cancer Biology Faculty Papers

Cyclin D1 promotes nuclear DNA synthesis through phosphorylation and inactivation of the pRb tumor suppressor. Herein, cyclin D1 deficiency increased mitochondrial size and activity that was rescued by cyclin D1 in a Cdk-dependent manner. Nuclear respiratory factor 1 (NRF-1), which induces nuclear-encoded mitochondrial genes, was repressed in expression and activity by cyclin D1. Cyclin D1-dependent kinase phosphorylates NRF-1 at S47. Cyclin D1 abundance thus coordinates nuclear DNA synthesis and mitochondrial function.


The Acute Effects Of Nut Ingestion On Plasma Levels Of Polyphenol Compounds, Biomarkers Of Antioxidant Status, And Lipid Peroxidation, Setareh Torabian Esfahani Aug 2006

The Acute Effects Of Nut Ingestion On Plasma Levels Of Polyphenol Compounds, Biomarkers Of Antioxidant Status, And Lipid Peroxidation, Setareh Torabian Esfahani

Loma Linda University Electronic Theses, Dissertations & Projects

Nuts are rich sources of polyphenolic compounds and nutrients, which have antioxidant capacity. To assess the acute effect of treatment diet (75% of energy from nuts (walnut or almond) and control diet (habitual diet with no nut consumption) in healthy subjects on plasma total phenol content, antioxidant capacity and plasma lipid peroxidation. Thirteen subjects participated in the crossover design study. After an overnight fast, walnut, almond and a control diet, in form of smoothies, were consumed by the study subjects. Each subject participated on three occasions one week apart, consuming one of the smoothies each time. Blood samples were obtained …


Factors That Influence The Blood Flow Response Of Skin To Electrical Stimulation, Abdul-Majeed Raja Al-Malty Jun 2006

Factors That Influence The Blood Flow Response Of Skin To Electrical Stimulation, Abdul-Majeed Raja Al-Malty

Loma Linda University Electronic Theses, Dissertations & Projects

Female reproductive hormones, aging, global heating and local heating are factors affecting skin blood flow (SBF), but their effect on electrical stimulation (ES) has never been examined until the present investigation. To investigate female reproductive hormones, nine women (age= 25.6±3.5 years) with a normal menstrual cycle (MC) underwent ES in thermoneutral (25°±0.5°C) and warm environments (35°±0.5°C). To investigate aging, ES was applied on active young (n=15, age=32.1±8.3 years) and old (n=8, 64.5±6.2 years) groups in thermoneutral and warm environments. To investigate the effect of global and local heating, groups of 15 and 18 subjects (age= 18-40 years) experienced ES under …


In Vitro Expression And Purification Of Class I Mhc Molecules, Loi Cheng May 2006

In Vitro Expression And Purification Of Class I Mhc Molecules, Loi Cheng

Honors Scholar Theses

The major histocompatibility complex (MHC) is a gene family responsible for many critical functions of the immune system in most vertebrates. The MHC consists of three classes differentiated by their structure and function, and MHC class I encodes antigen binding proteins as well as chaperone and accessory proteins such as tapasin. The purpose of this project is to reconstitute several human MHC class I molecules in their peptide-filled and peptide-deficient forms, and to purify these proteins for biochemical study. The expressed proteins include wild type and mutant variants of the fusion protein human leukocyte antigen HLA-B*0801-fos, and human beta-2-microglobulin (β2m). …


Role Of Caveolin-1 In The Regulation Of The Vascular Shear Stress Response, Philippe G. Frank, Michael P. Lisanti May 2006

Role Of Caveolin-1 In The Regulation Of The Vascular Shear Stress Response, Philippe G. Frank, Michael P. Lisanti

Department of Cancer Biology Faculty Papers

In blood vessels, endothelia are submitted to constant shear effects and are, under normal conditions, capable of responding to any variation in hemodynamic forces. Caveolae — 50- to 100-nm plasma membrane invaginations present at the surface of terminally differentiated cells and particularly enriched in ECs — are composed of a high sphingolipid and cholesterol content and the protein caveolin-1 (Cav-1). Previous studies have suggested that caveolae and endothelial Cav-1 may regulate the vascular response to altered shear stress. In this issue of the JCI, Yu et al. have examined the role of Cav-1/caveolae in the regulation of flow-induced alterations (i.e., …


Aspartyl-Trna Synthetase Is The Target Of Peptidenucleotide Antibiotic Microcin C, Anastasia Metlitskaya, Teymur Kazakov, Aigar Kommer, Olga Pavlova, Mette Praetorius-Ibba, Michael Ibba, Igor Krasheninnkov, Vyacheslav Kolb, Inessa Khmel, Konstantin Severinov Mar 2006

Aspartyl-Trna Synthetase Is The Target Of Peptidenucleotide Antibiotic Microcin C, Anastasia Metlitskaya, Teymur Kazakov, Aigar Kommer, Olga Pavlova, Mette Praetorius-Ibba, Michael Ibba, Igor Krasheninnkov, Vyacheslav Kolb, Inessa Khmel, Konstantin Severinov

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Microcin C is a ribosome-synthesized heptapeptide that contains a modified adenosine monophosphate covalently attached to the C-terminal aspartate. Microcin C is a potent inhibitor of bacterial cell growth. Based on the in vivo kinetics of inhibition of macromolecular synthesis, Microcin C targets translation, through a mechanism that remained undefined. Here, we show that Microcin C is a subject of specific degradation inside the sensitive cell. The product of degradation, a modified aspartyl-adenylate containing an N-acylphosphoramidate linkage, strongly inhibits translation by blocking the function of aspartyl-tRNA synthetase.


C To U Editing Stimulates A To I Editing In The Anticodon Loop Of A Cytoplasmic Threonyl Trna In Trypanosoma Brucei, Mary Anne T. Rubio, Frank L. Ragone, Kirk W. Gaston, Michael Ibba, Juan D. Alfonzo Jan 2006

C To U Editing Stimulates A To I Editing In The Anticodon Loop Of A Cytoplasmic Threonyl Trna In Trypanosoma Brucei, Mary Anne T. Rubio, Frank L. Ragone, Kirk W. Gaston, Michael Ibba, Juan D. Alfonzo

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Editing of tRNAs is widespread in nature and either changes the decoding properties or restores the folding of a tRNA. Unlike the phylogenetically disperse adenosine (A) to inosine (I) editing, cytosine (C) to uridine (U) editing has only been previously described in organellar tRNAs. We have shown that cytoplasmic tRNAThr(AGU) undergoes two distinct editing events in the anticodon loop: C to U and A to I. In vivo, every inosine-containing tRNAThr is also C to U edited at position 32. In vitro, C to U editing stimulates conversion of A to I at the wobble base. Although …


Simultaneous Measurement Of Water Volume And Ph In Single Cells Using Bcecf And Fluorescence Imaging Microscopy, Francisco J. Alvarez-Leefmans, José J. Herrera-Pérez, Martín S. Márquez, Victor M. Blanco Jan 2006

Simultaneous Measurement Of Water Volume And Ph In Single Cells Using Bcecf And Fluorescence Imaging Microscopy, Francisco J. Alvarez-Leefmans, José J. Herrera-Pérez, Martín S. Márquez, Victor M. Blanco

Pharmacology and Toxicology Faculty Publications

Regulation and maintenance of cell water volume and intracellular pH (pHi) are vital functions that are interdependent; cell volume regulation affects, and is in turn affected by, changes in pHi. Disruption of either function underlies various pathologies. To study the interaction and kinetics of these two mechanisms, we developed and validated a quantitative fluorescence imaging microscopy method to measure simultaneous changes in pHi and volume in single cells loaded with the fluorescent probe BCECF. CWV is measured at the excitation isosbestic wavelength, whereas pHiis determined ratiometrically. The method has a time resolution of …


A Case-Control Study Of Farming And Prostate Cancer In African-American And Caucasian Men, Tamra E. Meyer, Ann L. Coker, Maureen Sanderson, Elaine Symanski Jan 2006

A Case-Control Study Of Farming And Prostate Cancer In African-American And Caucasian Men, Tamra E. Meyer, Ann L. Coker, Maureen Sanderson, Elaine Symanski

CRVAW Faculty Journal Articles

Objective: To determine the risk of prostate cancer associated with farming by duration, recency and specific activities among African-Americans and Caucasians.

Methods: This population-based case–control study had information on farming-related activities for 405 incident prostate cancer cases and 392 controls matched for age, race and region in South Carolina, USA, from 1999 to 2001. Cases with histologically confirmed, primary invasive prostate cancer who were aged between 65 and 79 years were ascertained through the South Carolina Central Cancer Registry. Appropriately matched controls were identified from the Health Care Financing Administration Medicare Beneficiary File. Data were collected using computer-assisted telephone interviewing, …


Need For Cognition And Message Complexity In Motivating Fruit And Vegetable Intake Among Callers To The Cancer Information Service, Pamela Williams-Piehota, Judith Pizarro, Stephanie A. Navarro Silvera, Linda Mowad, Peter Salovey Jan 2006

Need For Cognition And Message Complexity In Motivating Fruit And Vegetable Intake Among Callers To The Cancer Information Service, Pamela Williams-Piehota, Judith Pizarro, Stephanie A. Navarro Silvera, Linda Mowad, Peter Salovey

Department of Public Health Scholarship and Creative Works

This field experiment examined the impact of an individual's need for cognition (NFC; the tendency to enjoy thinking deeply about issues), complex versus simple messages, and the interaction of NFC and message type on encouraging fruit and vegetable consumption. Callers to the Cancer Information Service of the National Cancer Institute (N = 517) were asked to participate in the experiment at the end of their call. Individual NFC was assessed, and participants were assigned randomly to receive a telephone message promoting fruit and vegetable consumption that was either complex and multifaceted or simple and straightforward. Similarly constructed brochures were …


Heparin Modulates The 99-Loop Of Factor Ixa: Effects On Reactivity With Isolated Kunitz-Type Inhibitor Domains, Pierre F. Neuenschwander, Stephen R. Williamson, Armen Nalian, Kimberly J. Baker-Deadmond Jan 2006

Heparin Modulates The 99-Loop Of Factor Ixa: Effects On Reactivity With Isolated Kunitz-Type Inhibitor Domains, Pierre F. Neuenschwander, Stephen R. Williamson, Armen Nalian, Kimberly J. Baker-Deadmond

Faculty Publications

Reactivity of factor IXa with basic pancreatic trypsin inhibitor is enhanced by low molecular weight heparin (enoxaparin). Previous studies by us have suggested that this effect involves allosteric modulation of factor IXa. We examined the reactivity of factor IXa with several isolated Kunitz-type inhibitor domains: basic pancreatic trypsin inhibitor, the Kunitz inhibitor domain of protease Nexin-2, and the first two inhibitor domains of tissue factor pathway inhibitor. We find that enhancement of factor IXa reactivity by enoxaparin is greatest for basic pancreatic trypsin inhibitor (>10-fold), followed by the second tissue factor pathway inhibitor domain (1.7-fold) and the Kunitz inhibitor …


Effects Of Ascorbic Acid On Impaired Vascular Reactivity In Aortas Isolated From Age-Matched Hypertensive And Diabetic Rats, Mohd Rais Mustafa, Macha Ajay Jan 2006

Effects Of Ascorbic Acid On Impaired Vascular Reactivity In Aortas Isolated From Age-Matched Hypertensive And Diabetic Rats, Mohd Rais Mustafa, Macha Ajay

Mohd Rais Mustafa

Impaired vascular reactivity is a hallmark of several cardiovascular diseases that include hypertension and diabetes. This study compared the changes in vascular reactivity in age-matched experimental hypertension and diabetes, and, subsequently, tested whether these changes could be affected directly by ascorbic acid (10 microM). Endothelium-derived nitric oxide (NO) modulation of ascorbic acid effects was also investigated. All the experiments were performed in the presence of a cyclooxygenase inhibitor, indomethacin (10 microM). Results showed that the endothelium-dependent and -independent relaxations induced by acetylcholine (ACh) and sodium nitroprusside (SNP), respectively, were blunted to a similar extent in isolated aortic rings from age-matched …


Bioassay-Guided Isolation Of A Vasorelaxant Active Compound From Kaempferia Galanga L, Mohd Rais Mustafa, Khalijah Awang, Mustafa Ali Mohd, Rozana Othman, Halijah Ibrahim Jan 2006

Bioassay-Guided Isolation Of A Vasorelaxant Active Compound From Kaempferia Galanga L, Mohd Rais Mustafa, Khalijah Awang, Mustafa Ali Mohd, Rozana Othman, Halijah Ibrahim

Mohd Rais Mustafa

Bioassay-guided fractionation was performed on a crude dichloromethane extract of Kaempferia galanga L. using chromatography techniques. Screening of the extract for biological activity started with the brine shrimp lethality bioassay, followed by the study of its antihypertensive activity on anaesthetized rats, which involved monitoring of the extract's effect on mean arterial blood pressure. The components of the fractions obtained from the separation procedures were analyzed using gas chromatography (GC). The yield of the CH2Cl2 extract was 0.29% of the crude plant extract. Analysis of the data for brine shrimp lethality test using the Finney computer program showed that this extract …


A Mechanistic Study Of The Protective Effects Of S-Adenosyl-L-Methionine Against Hepatotoxicity Of Acetaminophen, Marcus V. Terneus Jr. Jan 2006

A Mechanistic Study Of The Protective Effects Of S-Adenosyl-L-Methionine Against Hepatotoxicity Of Acetaminophen, Marcus V. Terneus Jr.

Theses, Dissertations and Capstones

Hepatic toxicity is known to be associated with excessive doses of the over-the-counter analgesic, acetaminophen (APAP). APAP overdose is the leading cause of drug-induced liver failure in the United States. APAP hepatotoxicity is dependent on the biotransformation of APAP by cytochrome P450 to the toxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI). APAP, when taken in excessive doses, can lead to severe liver damage with the potential to progress to liver failure. Despite substantial efforts in past studies, the mechanism by which APAP induces such damaging effects is not completely understood. Recent discoveries suggest that glutathione (GSH) depletion, protein alkylation and reactive metabolite …


Synthesis And In Vitro Binding Of N,N-Dialkyl-2-Phenylindol-3-Ylglyoxylamides For The Peripheral Benzodiazepine Binding Sites, T. P. Homes, F. Mattner, Paul A. Keller, A. Katsifis Jan 2006

Synthesis And In Vitro Binding Of N,N-Dialkyl-2-Phenylindol-3-Ylglyoxylamides For The Peripheral Benzodiazepine Binding Sites, T. P. Homes, F. Mattner, Paul A. Keller, A. Katsifis

Faculty of Science - Papers (Archive)

A series of N,N-dialkyl-2-phenylindol-3-ylglyoxylamides bearing the halogens iodine and bromine were synthesised and their binding affinity for the peripheral benzodiazepine binding sites (PBBS) in rat kidney mitochondrial membranes were evaluated using [3H]-PK11195. Central benzodiazepine receptor (CBR) affinities were also evaluated in rat cortices using 3H-flumazenil to determine their selectivity for PBBS over CBR. The tested compounds had PBBS binding affinities (IC50) ranging from 7.86 nM to 618 nM, with all compounds showing high selectivity over the CBR (CBR IC50 > 5000 nM). Among the 12 compounds tested, those with a diethylamide group were the most potent. The highest affinity iodinated PBBS …


Identification Of Novel Allosteric Regulators Of Human Erythrocyte Pyruvate Kinase, Shilpa S. Kharalkar Jan 2006

Identification Of Novel Allosteric Regulators Of Human Erythrocyte Pyruvate Kinase, Shilpa S. Kharalkar

Theses and Dissertations

Erythrocyte pyruvate kinase (R-PK) is a key glycolytic enzyme catalyzing the transphosphorylation of phosphoenolpyruvate (PEP) and ADP to pyruvate and ATP respectively3,4. The substrate PEP and product pyruvate of this reaction are involved in a number of energetic and biosynthetic pathways; hence a tight regulation of R-PK activity is crucial not only for glycolysis, but also for the entire cellular metabolism. Deficiency of R-PK is one of the most common enzymatic defects of RBC, and may be caused by mutations of the PK-LR (pyruvate kinase liver red blood cell) gene31, 32. Clinically, R-PK deficiency manifests itself as a chronic life-long …


Discovery Of Lignin Sulfate As A Potent Inhibitor Of Hsv Entry Into Cells, Jay N. Thakkar Jan 2006

Discovery Of Lignin Sulfate As A Potent Inhibitor Of Hsv Entry Into Cells, Jay N. Thakkar

Theses and Dissertations

The herpes virus family consists of more than hundred members that infect organisms, of which eight, differing markedly in the biology are known to infect humans. HSV- I is the most common one, causing oral lesions and sporadic encephalitis. These infections are highly prevalent affecting at least one in three individuals in the United States.The entry of the herpes virus into the cell is a two-step process. The initial step involves the cell surface heparan sulfate and glycoproteins in the viral envelope which enables the virus to penetrate into the cell. The second step is the fusion step. Depending on …


Reproducing Published Results From In Silico Computer Models Of The Acute Inflammatory Response To Severe Sepsis, Wayne W. Wakeland, Joe Fusion, Brahm Goldstein Jan 2006

Reproducing Published Results From In Silico Computer Models Of The Acute Inflammatory Response To Severe Sepsis, Wayne W. Wakeland, Joe Fusion, Brahm Goldstein

Systems Science Faculty Publications and Presentations

Recent studies describe computer simulation models of the acute or systemic inflammatory response (AIR or SIR) to severe sepsis, a condition that can lead to multiple organ failure and death. One study used an agent-based model, while the other used differential equations (DEs) to simulate a randomized clinical trial. Both studies obtained results similar to the actual results from a successful clinical drug trial of severe sepsis, suggesting that in silico (simulated) randomized clinical trials may be used to design more effective in vivo clinical trials.


Cost Prevention Of Hiv, Jerika Lam Jan 2006

Cost Prevention Of Hiv, Jerika Lam

Pharmacy Faculty Articles and Research

"Since the introduction of highly active antiretroviral therapy (HAART) in the late 1990s, management of patients with human immunodeficiency virus (HIV) infection has improved where they are living longer and with fewer incidences of opportunistic illnesses. Furthermore, significant progress has been made in the understanding of the disease, the ability to quantify viral load and correlate with clinical outcomes, genotypic and phenotypic resistance assays designed to assess viral susceptibility, and a heightened awareness and appreciation of the importance of treatment adherence to ensure virologic suppression.' In spite of the benefits that HIV-infected patients may have acquired in terms of more …


Methods For The Study Of Signaling Molecules In Membrane Lipid Rafts And Caveolae, Rennolds S. Ostrom, Paul A. Insel Jan 2006

Methods For The Study Of Signaling Molecules In Membrane Lipid Rafts And Caveolae, Rennolds S. Ostrom, Paul A. Insel

Pharmacy Faculty Articles and Research

Lipid rafts and caveolae are cholesterol- and sphingolipid-rich microdomains of the plasma membrane that concentrate components of certain signal transduction pathways. Interest in and exploration of these microdomains has grown in recent years, especially after the discovery of the biochemical marker of caveolae, caveolin, and the recognition that caveolin interacts with many different signaling molecules via its scaffolding domain. There are three major types of caveolins (1, 2, and 3), with some selectivity in their expression in different tissues. Results assessing lipid raft/caveolae co-localization of molecules in signal transduction pathways have provided support for the idea that signaling components are …


Introduction To N-Adaptive Fuzzy Models To Analyze Public Opinion On Aids, Florentin Smarandache, W.B. Vasantha Kandasamy Jan 2006

Introduction To N-Adaptive Fuzzy Models To Analyze Public Opinion On Aids, Florentin Smarandache, W.B. Vasantha Kandasamy

Branch Mathematics and Statistics Faculty and Staff Publications

“AIDS is not simply a physical malady, it is also an artifact of social and sexual transgression, violated taboo, fractured identity—political and personal projections. Its key words are primarily the property of the powerful. AIDS: Keywords – is my attempt to identify and contest some of the assumptions underlying our current ‘knowledge’. In this effort I am joined by many AIDS activists including people living with AIDS— Acquired Immuno Deficiency Syndrome. “A syndrome is a pattern of symptoms pointing to a “morbid state” which may or may not be caused by infectious agents; a disease, on the other hand is, …


2,6-Hexadecadiynoic Acid And 2,6-Nonadecadiynoic Acid - Novel Synthesized Acetylenic Fatty Acids As Potent Antifungal Agents, Nestor Carballeira, David Sanabria, Clarisa Cruz, Keykavous Parang, Baojie Wan, Scott Franzblau Jan 2006

2,6-Hexadecadiynoic Acid And 2,6-Nonadecadiynoic Acid - Novel Synthesized Acetylenic Fatty Acids As Potent Antifungal Agents, Nestor Carballeira, David Sanabria, Clarisa Cruz, Keykavous Parang, Baojie Wan, Scott Franzblau

Pharmacy Faculty Articles and Research

The hitherto unknown 2,6-hexadecadiynoic acid, 2,6-nonadecadiynoic acid, and 2,9-hexadecadiynoic acid were synthesized in two steps and in 11–18% overall yields starting from either 1,5-hexadiyne or 1,8-nonadiyne. Among all the compounds 2,6-hexadecadiynoic acid displayed the best overall antifungal activity against both the fluconazole resistant Candida albicans strains ATCC 14053 and ATCC 60193 (MIC = 11 μM) and against Cryptococcus neoformans ATCC 66031 (MIC < 5.7 μM). The 2,9-hexadecadiynoic acid did not display any significant cytotoxicity against the fluconazole resistant C. albicans strains, but it showed fungitoxicity against C. neoformans ATCC 66031 with a MIC value of <5.8 μM. Other fatty acids, such as 2-hexadecynoic acid, 5-hexadecynoic acid, 9-hexadecynoic acid, and 6-nonadecynoic acid were also synthesized and their antifungal activities compared. The 2-hexadecynoic acid, a known antifungal fatty acid, exhibited the best antifungal activity (MIC = 9.4 μM) against the fluconazole resistant C. albicans ATCC 14053 strain, but it showed a MIC value of only 100 μM against C. albicans ATCC 60193. The fatty acids 2,6-hexadecadiynoic acid and 2-hexadecynoic acid also displayed a MIC of 140–145 μM towards Mycobacterium tuberculosis H37Rv in Middlebrook 7H12 medium. In conclusion, 2,6-hexadecadiynoic acid exhibited the best fungitoxicity profile compared to other analogues. This diynoic fatty acid has the potential to be further evaluated for use in topical antifungal formulations.


Linking Ligand-Induced Alterations In Androgen Receptor Structure To Differential Gene Expression: A First Step In The Rational Design Of Selective Androgen Receptor Modulators, Dmitri Kazmin, Tatiana Prytkova, C. Edgar Cook, Russell Wolfinger, Tzu-Ming Chu, David Beratan, J. D. Norris, Ching-Yi Chang, Donald P. Mcdonnell Jan 2006

Linking Ligand-Induced Alterations In Androgen Receptor Structure To Differential Gene Expression: A First Step In The Rational Design Of Selective Androgen Receptor Modulators, Dmitri Kazmin, Tatiana Prytkova, C. Edgar Cook, Russell Wolfinger, Tzu-Ming Chu, David Beratan, J. D. Norris, Ching-Yi Chang, Donald P. Mcdonnell

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

We have previously identified a family of novel androgen receptor (AR) ligands that, upon binding, enable AR to adopt structures distinct from that observed in the presence of canonical agonists. In this report, we describe the use of these compounds to establish a relationship between AR structure and biological activity with a view to defining a rational approach with which to identify useful selective AR modulators. To this end, we used combinatorial peptide phage display coupled with molecular dynamic structure analysis to identify the surfaces on AR that are exposed specifically in the presence of selected AR ligands. Subsequently, we …