Chemicals and Drugs Commons^™

Hiv-1 Matrix Protein Binding To Rna, Ayna Alfadhli, Henry Mcnett, Seyram Tsagli, Hans Peter Bachinger, David H. Peyton

Chemistry Faculty Publications and Presentations

The matrix (MA) domain of the HIV-1 precursor Gag (PrGag) protein plays multiple roles in the viral replication cycle. One essential role is to target PrGag proteins to their lipid raft-associated phosphatidylinositol-(4,5)-bisphosphate (PI[4,5]P2) assembly sites at the plasma membranes (PMs) of infected cells. In addition to this role, several reports have implicated nucleic acid binding properties to retroviral MAs. Evidence indicates that RNA binding enhances the binding specificity of MA to PI(4,5)P2-containing membranes, and supports a hypothesis in which RNA binding to MA acts as a chaperone that protects MA from associating with inappropriate cellular membranes prior to PrGag delivery …

Relationship Of Vitamin D Levels To Blood Pressure In A Biethnic Cohort, Rosario O. Sakamoto

Loma Linda University Electronic Theses, Dissertations & Projects

Background: Serum hydroxyvitamin D [25(OH)D] has been well-accepted as not an ordinary vitamin but a pro-hormone that has many benefits beyond its well-known effects on bone. Cardiovascular risk factors such as hypertension remain a huge health burden and Blacks have been recognized to have higher prevalence of hypertension compared to non-Hispanic Whites. Despite increasing evidence of the benefits of vitamin D on blood pressure control, there is much more to be learned about the relationship of serum 25(OH)D to blood pressure among different ethnicities.

Purpose: The goal of this study was to determine whether vitamin D serum 25(OH)D levels were …

Determination Of Protein Using Microdrop Assay, Hardik Khared

All Capstone Projects

After purification of protein, it is important to know the concentration of protein in our samples. Concentration or amount of protein in the sample is determined by different assay as BCA (bicinchoninic acid) Assay, Bradford Assay, and Lowery Assay. There are different methods available to perform these assays, which have some limitations, restrictions, advantages and disadvantages. These methods require large amounts of costly reagents, proteins and most importantly, valuable time. To overcome these problems a new method is developed called Microdrop Protein Analysis. This new method required a very small amount of reagents and protein mixtures (2-5 µʅ volume) and …

Detection Of Protein By Microdrop Analysis, Yogeshkumar Radadiya

All Capstone Projects

Analysis of protein depends particularly on protein concentration. Protein concentration measurement is the most important part in the research work to conduct protein-related studies. Although there are many methods available for this purpose, each method has certain limitations. The aim of the experiment is to develop either new or modified analytical method for the analysis and detection of protein using newly introduced micro-plate reader equipped with Take-3 microplate with the help of Gen-5 software. An ideal assay should be simple and easy to carry out. Another aspect to be taken into consideration are low inference, stability of measured components and …

The Release Of Calcium In Bacillus Anthracis Pathogenicity, Natiera Magnuson, Manomita Patra, Maria Elena Reynaga, Ernesto Abel-Santos

McNair Poster Presentations

Bacillus anthracis spores form in response to starvation and can withstand extremes of heat, radiation, and chemical toxins, making B. anthracis spores ideal vehicles for infections.1 The resistance and dormancy of bacterial spores are dependent on a largely dehydrated core.2 The spore core is not only devoid of water, but contains between 0.8 to 1M calcium complexed with 2,6-pyridinedicarboxylic acid (dipicolinic acid, DPA). The DPA-calcium complex (CaDPA) helps protect DNA, RNA, and the metabolic enzymes needed for the establishment of a vegetative cell cytoplasm.3 An anthrax infection starts with the germination of B. anthracis spores in a macrophage.4 The germinated …

Development And Validation Of A Rapid Multi-Class Method For The Confirmation Of Fourteen Prohibited Medicinal Additives In Pig And Poultry Compound Feed By Liquid Chromatography Tandem Mass Spectrometry, Mark Cronly, Patrice Behan, Barry Foley, Liam Regan, Marella Gallagher, Sean Earley, Paula Shearan, Edward Malone

Articles

A confirmatory method has been developed to allow for the analysis of fourteen prohibited medicinal additives in pig and poultry compound feed. These compounds are prohibited for use as feed additives although some are still authorised for use in medicated feed. Feed samples are extracted by acetonitrile with addition of sodium sulphate. The extracts undergo a hexane wash to aid with sample purification. The extracts are then evaporated to dryness and reconstituted in initial mobile phase. The samples undergo an ultracentrifugation step prior to injection onto the LC-MS/MS system and are analysed in a run time of 26 minutes. The …

Total Protein Determination Using Micro Plate Assay, Julie Ruffatti

All Capstone Projects

One of the largest challenges that food manufactures are facing today is the management of food allergens. Allergenic protein in trace amounts, part per million concentrations, will trigger a reaction in some individuals. Food manufacturers need to prevent allergen cross-contamination by performing adequate sanitation after production of an allergenic containing food. Allergen detection kits are used to determine if sufficient protein was removed from the equipment surfaces during sanitation. One kit on the market is the 3M™ Clean- Trace™ Surface Protein (Allergen) swab tests. The test qualitatively detects the presence of protein based on the biuret reaction and will yield …

Synthesis And Analytical Evaluation Of Folate Conjugates For Use In Cancer Cell Detection, Sneha Reddy Kuthuru

All Capstone Projects

Recent clinical studies have shown the importance of folate receptor in drug delivery system as they increase the potency and reduce toxicity of many cancer therapies. The folate receptor alpha ( FR-a) binds with high affinity for folic acid and serves for receptor mediated transport of folate into cells. Folate is necessary for DNA metabolism and thus it is speculated that rapidly dividing cancer cells have an increased requirement for folic acid. It is known that FR-a levels are elevated in specific malignant diseases (solid tumors, leukemia) and thus the FR receptor serves as useful targeting moiety for the diagnosis …

High Pressure Liquid Chromatography Studies Of The Reaction Of Platinum Complexes With Peptides, Khaja Muneeruddin

Masters Theses & Specialist Projects

Platinum complexes (cisplatin, carboplatin and oxaliplatin) are effective anticancer agents. However the major drawbacks of platinum chemotherapy are toxic side effects and resistance. The affinity of platinum complexes to sulfur donor ligands of side chains of methionine and cysteine amino acids was assumed to be responsible for toxicity and resistance. Recently, it was found that the reaction of platinum complex with proteins containing sulfur donor ligands could actually favor its anticancer activity. Copper transporter 1 (Ctr 1), a protein involved in the transport of copper into the cell, also helps in the influx of cisplatin by binding to N-terminal domain …

4 Part Research Project: Cholecystokinin, Marcie Tasker

Academic Symposium of Undergraduate Scholarship

This 4 part research paper contains information on the biological molecule Cholecystokinin. The following research discusses and presents evidence of the name, history and structure of the hormone. It also discusses the different chemical reactions Cholecystokinin has in the body, the biological roles of Cholecystokinin and the importance of Cholecystokinin focusing specifically on the unexplained obesity issue of our world.

Predicting Flavonoid Ugt Regioselectivity With Graphical Residue Models And Machine Learning., Arthur Rhydon Jackson

Electronic Theses and Dissertations

Machine learning is applied to a challenging and biologically significant protein classification problem: the prediction of flavonoid UGT acceptor regioselectivity from primary protein sequence. Novel indices characterizing graphical models of protein residues are introduced. The indices are compared with existing amino acid indices and found to cluster residues appropriately. A variety of models employing the indices are then investigated by examining their performance when analyzed using nearest neighbor, support vector machine, and Bayesian neural network classifiers. Improvements over nearest neighbor classifications relying on standard alignment similarity scores are reported.

Proteomic And Phospho-Proteomic Profile Of Human Platelets In Basal, Resting State: Insights Into Integrin Signaling, Amir H. Qureshi, Vineet Chaoji, Dony Maiguel, Mohd Hafeez Faridi, Constantinos J. Barth, Saeed M. Salem, Mudita Singhal, Darren Stoub, Bryan Krastins, Mitsunori Ogihara, Mohammed J. Zaki, Vineet Gupta

Faculty Work Comprehensive List

During atherogenesis and vascular inflammation quiescent platelets are activated to increase the surface expression and ligand affinity of the integrin αIIbβ3 via inside-out signaling. Diverse signals such as thrombin, ADP and epinephrine transduce signals through their respective GPCRs to activate protein kinases that ultimately lead to the phosphorylation of the cytoplasmic tail of the integrin αIIbβ3 and augment its function. The signaling pathways that transmit signals from the GPCR to the cytosolic domain of the integrin are not well defined. In an effort to better understand these pathways, we employed a combination of proteomic profiling and computational analyses of isolated …

Spiroadamantyl 1,2,4-Trioxolane, 1,2,4-Trioxane, And 1,2,4-Trioxepane Pairs: Relationship Between Peroxide Bond Iron(Ii) Reactivity, Heme Alkylation Efficiency, And Antimalarial Activity, Xiaofang Wang, Darren J. Creek, Yuxiang Dong, Jacques Chollet, Christian Scheurer, Sergio Wittlin, Susan A. Charman, Patrick H. Dussault, James K. Wood, Jonathan L. Vennerstrom

Chemistry Faculty Publications

These data suggest that iron(II) reactivity for a set of homologous spiroadamantyl 1,2,4-trioxolane, 1,2,4-trioxane, and 1,2,4-trioxepane peroxide heterocycles is a necessary, but insufficient, property of animalarial peroxides. Heme alkylation efficiency appears to give a more accurate prediction of antimalarial activity than FeSO4-mediated reaction rates, suggesting that antimalarial activity is not merely dependent on peroxide bond cleavage, but also on the ability of reactive intermediates to alkylate heme or other proximal targets.

Identifying Biomarkers For Resistance To Novel Cisplatin Analogues In Human Lung, Breast And Prostate Cancers, Becky Michelle Hess

UNLV Theses, Dissertations, Professional Papers, and Capstones

Cisplatin is a common therapeutic agent used in cancer treatment. Unfortunately, resistance to cisplatin in addition to severe side effects limits its use in cancer treatment. Two novel cisplatin analogues, 4DB and 4TB were shown to have varying cytotoxicity in lung, breast and prostate cancer cells. The hypothesis for this study states that the differences in 4DB and 4TB cytotoxicity among different tissue types is due to the type and efficiency of DNA repair mechanisms involved in response to these drugs.

To test the hypothesis, proteins involved in the rate limiting step of nucleotide excision repair (NER) and mismatch repair …

Multimeric Hemicellulases Facilitate Biomass Conversion, Zhanmin Fan, Kurt Wagschal, Wei Chen, Michael D. Montross, Charles C. Lee, Ling Yuan

Plant and Soil Sciences Faculty Publications

Two highly active trifunctional hemicellulases were constructed by linking the catalytic portion of a xylanase with an arabinofuranosidase and a xylosidase, using either flexible peptide linkers or linkers containing a cellulose-binding domain. The multifunctional enzymes retain the parental enzyme properties and exhibit synergistic effects in hydrolysis of natural xylans and corn stover.

Understanding The Physical Properties That Control Protein Crystallization By Analysis Of Largescale Experimental Data, W. Nicholson Price Ii, Yang Chen, Samuel K. Handelman, Helen Neely, Philip Manor, Richard Karlin, Rajesh Nair, Jinfeng Liu, Michael Baran, John Everett, Saichiu N. Tong, Farhad Forouhar, Swarup S. Swaminathan, Thomas Acton, Rong Xiao, Joseph R. Luft, Angela Lauricella, George T. Detitta, Burkhard Rost, Gaetano T. Montelione, John T. Hunt

Law Faculty Scholarship

Crystallization is the most serious bottleneck in high-throughput protein-structure determination by diffraction methods. We have used data mining of the large-scale experimental results of the Northeast Structural Genomics Consortium and experimental folding studies to characterize the biophysical properties that control protein crystallization. This analysis leads to the conclusion that crystallization propensity depends primarily on the prevalence of well-ordered surface epitopes capable of mediating interprotein interactions and is not strongly influenced by overall thermodynamic stability. We identify specific sequence features that correlate with crystallization propensity and that can be used to estimate the crystallization probability of a given construct. Analyses of …

Probing The Urea Dependence Of Residual Structure In Denatured Human Α-Lactalbumin, Victoria A. Higman, Heike I. Rösner, Raffaella Ugolini, Lesley H. Greene, Christina Redfield, Lorna J. Smith

Chemistry & Biochemistry Faculty Publications

Backbone ¹⁵N relaxation parameters and ¹⁵N–¹H^N residual dipolar couplings (RDCs) have been measured for a variant of human α-lactalbumin (α-LA) in 4, 6, 8 and 10 M urea. In the α-LA variant, the eight cysteine residues in the protein have been replaced by alanines (all-Ala α-LA). This protein is a partially folded molten globule at pH 2 and has been shown previously to unfold in a stepwise non-cooperative manner on the addition of urea. ¹⁵N R₂ values in some regions of all-Ala α-LA show significant exchange broadening which is reduced as the urea …

The Association Of Maternal Intention To Breastfeed, Early Skin-To-Skin Mother/Infant Contact, And Exclusive Breastfeeding During The Maternity Hospital Stay, Leslie Mary Bramson

Loma Linda University Electronic Theses, Dissertations & Projects

Breastfeeding is the optimal method to nourish and nurture an infant. Exclusive breastfeeding rates in the United States have reached the goal of Healthy People 2010 that 75% of mother's breastfeed in the immediate postpartum period. Yet, less than 35% of San Bernardino county mothers and 47.7% of Riverside county mothers are exclusively breastfeeding during their maternity hospital stays, with as many as 50% of the infants being weaned from the breast in the first 14 days of life.

This prospective study examined archived data collected by Perinatal Services Network (PSN) of Loma Linda University Medical Center/Children's Hospital for the …

Unlv Magazine, Tony Allen, Afsha Bawany, Barbara Cloud, Holly Ivy De Vore, Gian Galassi, Matthew K. Jacobsen, Michelle Mouton, Erin O'Donnell, Shane Bevell, Cate Weeks

UNLV Magazine

No abstract provided.

Electrical Detection Of The Temperature Induced Melting Transition Of A Dna Hairpin Covalently Attached To Gold Interdigitated Microelectrodes, Greg P. Brewood, Yaswanth Rangineni, Daniel J. Fish, Ashwini Bhandiwad, David R. Evans, Raj Solanki, Albert S. Benight

Chemistry Faculty Publications and Presentations

The temperature induced melting transition of a self-complementary DNA strand covalently attached at the 5' end to the surface of a gold interdigitated microelectrode (GIME) was monitored in a novel, label-free, manner. The structural state of the hairpin was assessed by measuring four different electronic properties of the GIME (capacitance, impedance, dissipation factor and phase angle) as a function of temperature from 25 degrees C to 80 degrees C. Consistent changes in all four electronic properties of the GIME were observed over this temperature range, and attributed to the transition of the attached single-stranded DNA (ssDNA) from an intramolecular, folded …

The Effect Of Radiation And Repeated Sub-Culturing On Tgf-Β1 Signaling In Frtl-5 Cells, Cheryl G. Burrell

Loma Linda University Electronic Theses, Dissertations & Projects

From our ongoing in vitro studies using the Fisher Rat Thyroid cell line-5 (FRTL-5) we recorded accelerated growth, reduced follicularization and reduction in thyroxin release that occurred as the cells were repeatedly sub-cultured. We also recorded that these changes occurred earlier and more rapidly following radiation exposure. We determined that TGF-β1 production increased under both conditions. We hypothesized that alteration in the TGF-β1 signaling pathway contributed to the changes observed in the cellular properties of FRTL-5 cells. Our objective was to examine some of the players in the TGF-β1 signaling pathway to determine whether radiation and/or repeated subculturing promoted changes …

The Association Between Lifestyle Factors And Inflammatory Markers, Kerry Ann Stonebrook

Loma Linda University Electronic Theses, Dissertations & Projects

Background: Cardiovascular disease (CVD) is the leading cause of death for both men and women in the United States. While smoking, high blood pressure, and elevated cholesterol levels are established risk factors for CVD, inflammation is being evaluated as a potential independent risk factor. A key cytokine regulator of the inflammatory response, interleukin-1 (IL-1), has emerged as playing a particularly important role at the genetic level in determining the degree to which the inflammation pathway is turned on. How an individual’s genetic make-up affects inflammation, CVD risk, and response to lifestyle intervention is an area of research that is in …

Abstraction Of Dimensional Relevance Of Molecular Representation: Generation Of Novel Inhibitors Against Malarial Plasmodium Falciparum Plasmepsin Iv, Christopher B. Abdul-Wahid

Undergraduate Honors Theses

The malarial parasite Plasmodium falciparum is endemic to 50% of the world's population, killing three million people a year, many of whom are children under five years of age. Due in part to the development of malarial resistance to current drug therapies, novel drug targets are being sought. The malarial hemolytic aspartic protease Plasmepsins are such targets of rational drug design.

We are developing a methodology to rapidly generate combinatorial libraries of chemical structures using a one-dimensional representation (Simplified molecular input line entry specification (SMILES)) of a molecule, to automatically generate a minimized three-dimensional representation (SYBYLMOL2), and to screen this …

Coupling Coherence Distinguishes Structure Sensitivity In Protein Electron Transfer, Tatiana Prytkova, Igor V. Kurnikov, David Beratan

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Quantum mechanical analysis of electron tunneling in nine thermally fluctuating cytochrome b562 derivatives reveals two distinct protein-mediated coupling limits. A structure-insensitive regime arises for redox partners coupled through dynamically averaged multiple-coupling pathways (in seven of the nine derivatives) where heme-edge coupling leads to the multiple-pathway regime. A structure-dependent limit governs redox partners coupled through a dominant pathway (in two of the nine derivatives) where axial-ligand coupling generates the single-pathway limit and slower rates. This two-regime paradigm provides a unified description of electron transfer rates in 26 ruthenium-modified heme and blue-copper proteins, as well as in numerous photosynthetic proteins.

Flavin Charge Transfer Transitions Assist Dna Photolyase Electron Transfer, Spiros S. Skourtis, Tatiana Prytkova, David Beratan

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

This contribution describes molecular dynamics, semi-empirical and ab-initio studies of the primary photo-induced electron transfer reaction in DNA photolyase. DNA photolyases are FADH−-containing proteins that repair UV-damaged DNA by photo-induced electron transfer. A DNA photolyase recognizes and binds to cyclobutatne pyrimidine dimer lesions of DNA. The protein repairs a bound lesion by transferring an electron to the lesion from FADH−, upon photo-excitation of FADH− with 350–450 nm light. We compute the lowest singlet excited states of FADH− in DNA photolyase using INDO/S configuration interaction, time-dependent density-functional, and time-dependent Hartree-Fock methods. The calculations identify the lowest singlet excited state of FADH− …

Dna Multiplex Hybridization On Microarrays And Thermodynamic Stability In Solution: A Direct Comparison, Daniel J. Fish, M. Todd Horne, Greg P. Brewood, Jim P. Goodarzi, Saba Alemayehu, Ashwini Bhandiwad, Robert P. Searles, Albert S. Benight

Chemistry Faculty Publications and Presentations

Hybridization intensities of 30 distinct short duplex DNAs measured on spotted microarrays, were directly compared with thermodynamic stabilities measured in solution. DNA sequences were designed to promote formation of perfect match, or hybrid duplexes containing tandem mismatches. Thermodynamic parameters DeltaH degrees , DeltaS degrees and DeltaG degrees of melting transitions in solution were evaluated directly using differential scanning calorimetry. Quantitative comparison with results from 63 multiplex microarray hybridization experiments provided a linear relationship for perfect match and most mismatch duplexes. Examination of outliers suggests that both duplex length and relative position of tandem mismatches could be important factors contributing to …

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.

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, …

Phosphoproteomic Studies Of Smooth Muscle Contraction: Investigation Of Differential Phosphorylation In Relaxed/Contracted Rat Aortic Smooth Muscle Tissue Using Maldi-Tof Ms, Tonya M. Pekar

Theses, Dissertations and Capstones

Many human disorders are associated with the malfunction of smooth muscle tissue, or are related to the capabilities of its proper function—asthma, glaucoma, renal inefficiency, hypertension, and cardiovascular disease. Dysfunctional proteins are frequently implicated as the source of such disorders. As the second highest cause of death in the United States, the epidemic of cardiovascular disease makes the study of smooth muscle of utmost concern.

The capabilities of proteomics and mass spectrometry allow the entire proteome complement of a cell or tissue type to be analyzed at once. This investigation employs such techniques in an effort to better understand the …

Trace Analysis Of Organic Substances, Alan Giltinan

Theses

One of the major challenges facing the pharmaceutical industry is the control of the amount of trace contaminants during the manufacture of organic substances. Lowering the level of contamination improves the quality of the product and reduces possible side effects.

One of the main techniques used to detect trace contaminants is UV-VIS spectroscopy, where the unique absorption fingerprint of a chemical reveals its presence. UV-VIS absorption is based upon the Beer-Lambert Law. The critical point to note about this law is that the absorption is exponentially dependent on both the concentration of the absorber and the pathlength traversed by the …