Life Sciences Commons^™

Compartmentalization Of Hiv-1 In The Secondary Lymphoid Tissues, James Peter Gregson

Theses and Dissertations

Follicular dendritic cells (FDCs) reside in the lymphoid follicles of the secondary lymphoid tissues (sLTs). Following the infection of an individual with human immunodeficiency virus type 1 (HIV-1), viral particles are trapped in massive quantities on the surfaces of FDCs. HIV-1 viral compartments are cell types or tissues between which there is a restriction of virus flow. Compartmentalization of HIV-1 creates numerous sites within the body in which the virus can undergo independent evolution, giving rise to a more diverse total viral population. Given the sessile nature of the FDC, I hypothesized that contrary to common assumptions, FDC-trapped HIV-1 is …

Fluorescent Photoinduced Electron Transfer (Pet) Proton Sensors, Risper Nyabeta

Theses, Dissertations and Culminating Projects

Two new fluorescent photoinduced electron transfer (PET) proton sensors based on anthracene and pyrazoline chromophores have been prepared. The anthracene sensor was prepared through alkylation of 2-pyridylcarbinol with 9-chloromethylanthracene and the pyrazoline sensor was prepared through an aldol condensation of 4- carboxybenzaldehyde and acetylpyridine followed by reaction with phenylhydrazine. The fluorescence of these sensors is modulated by the initiation or quenching of a PET process between the chromophore and a receptor due to protonation. The synthesis, characterization and proton binding studies of the new sensors are reported in this thesis.

Studies On The Mechanisms Of Homolog Pairing And Sister Chromatid Cohesion During Drosophila Male Meiosis, Jian Ma

Masters Theses

Meiosis is a complex process involving one round of DNA replication followed by two rounds of cell divisions. The proper segregation of homologs at meiosis I and sister chromatids during meiosis II is essential for the survival of the offspring. Aberrant chromosome segregation at any stage of meiosis can lead to aneuploidy. Meiotic chromosome segregation without crossing over or chiasmata is a widespread but poorly understand chromosome segregation pathway. In male Drosophila meiosis the absence of recombination in chromosomes makes it easier to identify mutations which influence homologous chromosome pairing and segregation.

Modifier of Mdg4 in Meiosis (MNM), a protein …

Development Of Chemomechanical Functionalization And Nanografting On Silicon Surfaces, Michael Vernon Lee

Theses and Dissertations

Progress in chemomechanical functionalization was made by investigating the binding of molecules and surface coverage on the silicon surface, demonstrating functionalization of silicon with gases by chemomechanical means, analyzing atomic force microscopy probe tip wear in atomic force microscopy (AFM) chemomechanical nanografting, combining chemomechanical functionalization and nanografting to pattern silicon with an atomic force microscope, and extending chemomechanical nanografting to silicon dioxide. Molecular mechanics of alkenes and alkynes bound to Si(001)-2x1 as a model of chemomechanically functionalized surfaces indicated that complete coverage is energetically favorable and becomes more favorable for longer chain species. Scribing a silicon surface in the presence …

Synthesis Of Resveratrol And Its Analogs, Phase-Transfer Catalyzed Asymmetric Glycolate Aldol Reaction, And Total Synthesis Of 8,9-Methylamido-Geldanamycin, Jing Liu

Theses and Dissertations

The phytoalexin resveratrol and its acetyl analogs have been made using a decarbonylative Heck reaction. The acid chloride derived from 3,5-dihydroxybenzoic acid was coupled with suitable protected 4-hydroxystyrene in the presence of palladium acetate and N,N-bis-(2,6-diisopropylphenyl)-4,5-dihydro imidazolium chloride to give the substituted stilbene in good yield as the key step. Human HL-60 cell assays showed the 4'-acetyl resveratrol variant improved activity (ED50 17 μM) relative to resveratrol (24 μM). Cinchona phase-transfer catalysts (PTC) were developed for glycolate aldol reactions to give differentially protected 1,2-diol products. Silyl enol ether of diphenylmethoxy-2,5-dimethoxyacetophenone reacted to generate benzhydryl-protected products. O-Allyl trifluorobenzyl cinchonium hydrodifluoride (20 …

Synthesis And Antiviral Evaluation Of Some 3'-Carboxymethyl-3'-Deoxyadenosine Derivatives, Houguang Shi

Theses and Dissertations

3'-Carboxymethyl-3'-deoxyadenosine derivatives were prepared from 2'-O-TBDMS-3'-deoxy-3'-[(ethoxycarbonyl)methyl]adenosine (1) via simple and efficient procedures. Conversion of 1 to 5'-azido-2'-O-TBDMS-3', 5'-dideoxy -3'-[(ethoxycarbonyl) methyl] adenosine (4) was accomplished via a novel one-pot method employing 5'-activation (TosCl) followed by efficient nucleophilic displacement with tetramethylguanidinium azide. Compound 4 was converted to a 5'-[(N-methylcarbamoyl)amino] derivative (5) via one-pot reduction/acylation employing H2/Pd-C followed by treatment with p-nitrophenyl N-methylcarbamate. The latter step of this two-step process required an efficient source of p-nitrophenyl N-methylcarbamate, thus a highly efficient new method for preparing p-nitrophenyl N-alkylcarbamate was developed. N6-phenylcarbamoyl groups were introduced by treatment with phenylisocyanate, and an efficient new method for …

Catecholaminergic Control Of Mitogen-Activated Protein Kinase Signaling In Paraventricular Neuroendocrine Neurons In Vivo And In Vitro: A Proposed Role During Glycemic Challenges, Arshad M. Khan, Todd A. Ponzio, Graciela Sanchez-Watts, B. Glenn Stanley, Glenn I. Hatton, Alan G. Watts

Arshad M. Khan, Ph.D.

No abstract provided.

Characterization And Structure Of A Zn2+ And [2fe-2s]-Containing Copper Chaperone From Archaeoglobus Fulgidus, Matthew H. Sazinsky, Benjamin Lemoine, Maria Orofino, Roman Davydov, Krisztina Z. Bencze, Timothy L. Stemmler, Brian M. Hoffman, José M. Argüello, Amy C. Rosenzweig

Biochemistry and Molecular Biology Faculty Publications

Bacterial CopZ proteins deliver copper to P1B-type Cu+-ATPases that are homologous to the human Wilson and Menkes disease proteins. The genome of the hyperthermophile Archaeoglobus fulgidus encodes a putative CopZ copper chaperone that contains an unusual cysteine rich N-terminal domain of 130 amino acids in addition to a C-terminal copper-binding domain with a conserved CXXC motif. The N-terminal domain (CopZ-NT) is homologous to proteins found only in extremophiles and is the only such protein that is fused to a copper chaperone. Surprisingly, optical, electron paramagnetic resonance, and X-ray absorption spectroscopic data indicate the presence of a [2Fe-2S] cluster in CopZ-NT. …

Water. New Waters And New Life, Juan Enriquez

New England Journal of Public Policy

An excerpt from an article about life sciences taken from the proceedings of the Education for Public Inquiry and International Citizenship (EPIIC) Symposium held at Tufts University in Massachusetts in February 2005 is presented.

Ginger Facilitates Cholinergic Activity Possibly Due To Blockade Of Muscarinic Autoreceptors In Rat Stomach Fundus, Muhammad N. Ghayur, Adil H. Khan, Anwarul H. Gilani

Department of Biological & Biomedical Sciences

Ginger (Zingiber officinale) is a universally known food plant reputed for its medicinal use in gastrointestinal disorders as a prokinetic and laxative. We recently showed that 70% aqueous-methanolic extract of ginger (Zo.Cr) exhibits prokinetic activity in rats via activation of post-synaptic muscarinic M3 receptor in rat stomach fundus. In view of the physiological significance of pre-synaptic muscarinic M1 and M2 autoreceptors, this study was undertaken to further look into the possible mode of action of the prokinetic effect of ginger through inhibition of pre-synaptic muscarinic receptors. Isolated tissue bath experiments were performed with Sprague-Dawley rat stomach fundus strip preparations immersed …

Inhibition Of Nitric Oxide And Soluble Guanylyl Cyclase Signaling Affects Olfactory Neuron Activity In The Moth, Manduca Sexta, Caroline H. Wilson, Thomas A. Christensen, Alan J. Nighorn

Health Sciences and Kinesiology Faculty Articles

Nitric oxide is emerging as an important modulator of many physiological processes including olfaction, yet the function of this gas in the processing of olfactory information remains poorly understood. In the antennal lobe of the moth, Manduca sexta, nitric oxide is produced in response to odor stimulation, and many interneurons express soluble guanylyl cyclase, a well-characterized nitric oxide target. We used intracellular recording and staining coupled with pharmacological manipulation of nitric oxide and soluble guanylyl cyclase to test the hypothesis that nitric oxide modulates odor responsiveness in olfactory interneurons through soluble guanylyl cyclase-dependent pathways. Nitric oxide synthase inhibition resulted …

Regulation Of Cell Diameter, For3p Localization, And Cell Symmetry By Fission Yeast Rho-Gap Rga4p, Maitreyi Das, David J. Wiley, Saskia Medina, Helen A. Vincent, Michelle D. Larrea, Andrea Oriolo, Fulvia Verde

Chemistry and Physics Faculty Articles

Control of cellular dimensions and cell symmetry are critical for development and differentiation. Here we provide evidence that the putative Rho-GAP Rga4p of Schizosaccharomyces pombe controls cellular dimensions. rga4Δ cells are wider in diameter and shorter in length, whereas Rga4p overexpression leads to reduced diameter of the growing cell tip. Consistent with a negative role in cell growth control, Rga4p protein localizes to the cell sides in a “corset” pattern, and to the nongrowing cell tips. Additionally, rga4Δ cells show an altered growth pattern similar to that observed in mutants of the formin homology protein For3p. Consistent with …

Human Frataxin: Iron And Ferrochelatase Binding Surface, Krisztina Z. Bencze, Taejin Yoon, CéSar MilláN-Pacheco, Patrick B. Bradley, Nina Pastor, J. A. Cowan, Timothy L. Stemmler

Biochemistry and Molecular Biology Faculty Publications

The coordinated iron structure and ferrochelatase binding surface of human frataxin have been characterized to provide insight into the protein’s ability to serve as the iron chaperone during heme biosynthesis.

Asymmetric Dihydroxylation And Aziridination Of Allenes And Related Chemistry, Renmao Liu

Theses and Dissertations

A novel method for asymmetric synthesis of α-hydroxy ketone with excellent regio- and stereoselectivity has been established by the systematic investigation of asymmetric dihydroxylation of allenes. The efficiency of kinetic resolution of racemic allenes was also investigated by using the AD reaction on both 1,3-disubstituted and trisubstituted allenes. Steric effects, electronic effects and allene substitution are also discussed. Aziridines were formed by copper-catalyzed intramolecular nitrene addition to alkenes. The carbamate group was used as the tether between the alkene and the nitrene. Subsequent nucleophilic attack of the aziridine was accomplished using RSH, R2NH, N3-,or ROH as the nucleophile. This addition …

Microwave Absorption Of Patterned Arrays Of Nanosized Magnetic Stripes With Different Aspect Ratios, Leszek M. Malkinski, Minghui Yu, Andriy Vovk, Donald J. Scherer Ii, Leonard Spinu, Weilie Zhou, Scott L. Whittenburg, Zachary Davis, Jin-Seung Jung

Chemistry and Biochemistry Faculty Publications

Arrays consisting of nanosized stripes of Permalloy with different length-to-width ratios have been fabricated using electron beam nanolithography, magnetron sputtering, and lift-off process. These stripes have a thickness of , a width of , and different lengths ranging from . The stripes are separated by a distance of . Magnetization hysteresis loops were measured using a superconducting quantum interference device susceptometer. Microwave absorption at was determined by means of ferromagnetic resonance technique. The dependence of the resonant field on the angle between the nanostructure and the in-plane dc magnetic field indicates the presence of uniaxial magnetic anisotropy associated with the …

Towards Early State Disease Detection In Microdevices: Fabrication And Testing Of Micro Total Analysis Systems For Bioanalytical Applications, Tao Pan

Theses and Dissertations

The past few years have seen a rapid expansion in interest in the characterization of the entire complement of proteins, or proteome. Micro total analysis systems (μTAS) are an emerging promising method, offering rapid, sensitive and low sample consumption separations. I have demonstrated microchip capillary electrophoresis (CE) devices made of CaF2. New methods have been developed for micromachining enclosed capillaries in CaF2. CE analysis of fluorescently labeled amino acids was used to illustrate bioanalytical applications of these microdevices. Initial on-chip infrared spectroscopy results for qualitative analyte identification were achieved in microfluidic CaF2 channels. I have also shown the evaluation of …

Sem Analysis Of Glue Behavior When Bonding Glass Structures With Complex Geometries, Yuri Sikorski, Robert Cunningham, Herman Orgeron, Chris Schenck, Ali Zand

Chemistry & Biochemistry Presentations And Conference Materials

Bonding of glass has been studied for many years and is a mature technology today. However, the recent advances in bio-photonics and micro-fluidics, such as lab-on-a-chip devices, accentuate a need to provide reliable adhesion and sealing of components with extremely complex surface geometries. In many cases it is necessary to prevent the adhesives from leaking into microscopic channels, capillaries and holes. We present the Scanning Electron Microscopy study of adhesion of glass samples with complex surface features. Variety of adhesion conditions and procedures were tried and studied. The results demonstrate the possibility of controlled reliable adhesion and sealing without filling/obstructing …

Early Stage Detection Of Marine Oil Oxidation, Loren Lapointe

Honors Theses

A method involving overnight stir bar sorptive extraction (SBSE) headspace gas chromatography/mass spectrometry (GC/MS) in negative ion chemical ionization (NICI) mode was developed to determine the presence of aldehydes (cis-4-heptenal, trans,trans-2,4-heptadienal, trans-2-octenal, cis-6-nonenal, trans-2-cis-6-nonadienal, trans-2-nonenal, and trans,trans-2,4-decadienal) in fresh and aged commercial fish oil (untreated and treated with antioxidant blends). Aldehyde standards were quantifiable to >100ppb levels using this method. Only trans,trans-2,4-heptadienal was shown to be present in the commercial fish oil and its presence was used to compare the performance of the two different antioxidant treatments in the fish oil. Includes Powerpoint.

Stoichiometric Controls Of Mercury Dilution By Growth, Roxanne Karimi, Celia Y. Chen, Paul C. Pickhardt, Nicholas S. Fisher, Carol L. Folt

Dartmouth Scholarship

Rapid growth could significantly reduce methylmercury (MeHg) concentrations in aquatic organisms by causing a greater than proportional gain in biomass relative to MeHg (somatic growth dilution). We hypothesized that rapid growth from the consumption of high-quality algae, defined by algal nutrient stoichiometry, reduces MeHg concentrations in zooplankton, a major source of MeHg for lake fish. Using a MeHg radiotracer, we measured changes in MeHg concentrations, growth and ingestion rates in juvenile Daphnia pulex fed either high (C:P = 139) or low-quality (C:P = 1317) algae (Ankistrodesmus falcatus) for 5 d. We estimated Daphnia steady-state MeHg concentrations, using a …

Electronic Anisotropy Between Open Shell Atoms In First And Second Order Perturbation Theory, Gerrit C. Groenenboom, Xi Chu, R. Krems

Chemistry and Biochemistry Faculty Publications

The interaction between two atoms in states with nonzero electronic orbital angular momenta is anisotropic and can be represented by a spherical tensor expansion. The authors derive expressions for the first order (electrostatic) and second order (dispersion and induction) anisotropic interaction coefficients in terms of the multipole moments and dynamic polarizabilities of the atoms and show that a complete description of the second order interaction requires odd rank or "out-of-phase" polarizabilities. The authors relate the tensorial expansion coefficients to the adiabatic Born-Oppenheimer potentials of the molecule and show that there are linear, and in some cases nonlinear, constraints on the …

Biochemical Characteristics Of Inconsistent Free T₄ Assays, Kristofer S. Fritz

Loma Linda University Electronic Theses, Dissertations & Projects

Serum levels of free thyroxine (T₄) are helpful in the clinical evaluation of patients who are suspected of having thyroid disease, since free T₄ (unbound) is known to closely relate to hyper, eu and hypothyroidism. There are documented inconsistencies among commercially available direct free thyroxine immunoassays. The biochemical basis for these inconsistencies is not understood and has not been characterized. Direct free T₄ measurements have been linked to both T₄-binding serum protein concentrations and protein-bound T₄ concentrations. A free T₄ reference method using direct equilibrium dialysis radioimmunoassay has been well characterized. New …

Notch Regulation Of Human Breat Cancer Progression: Contrasting Roles For Notch Signaling, Christine F. O'Neill

Electronic Theses and Dissertations

Notch signaling is associated with activation of either oncogenic or tumor suppressor activities. The human mammary adenocarcinoma cell line, MDA-MB-231, was characterized in vitro and in xenografts in vivo to test the hypothesis that activation of Notch signaling regulates mammary tumor phenotype. Notch 1, Notch2, and Notch4 signaling was compared by stable expression of their constitutively active intracellular domains (ICD). Notch4 activation led to enhanced tumorigenicity, in addition to increased cell proliferation and survival in vitro, whereas the activation of Notch 1 or Notch2 decreased cell proliferation and survival, in which Notch2 increased apoptosis. Stably transfected cell lines were …

Iron Dysregulation And Inflammation In Alzheimer’S Disease, Shino D. Magaki

Loma Linda University Electronic Theses, Dissertations & Projects

Alzheimer’s disease (AD) is the most common form of senile dementia in the US and worldwide but the causes of its pathogenesis are currently unknown. In this study, we examined two processes that have been implicated in the early stages of AD and other forms of neurodegeneration, iron dysregulation and inflammation, both of which can promote the increased production of amyloid precursor protein (APP). We have measured different pools of brain iron in transgenic iron regulatory protein 2 knockout (IRP2-/-) mice in the early stages of neurodegeneration and in affected brain regions from AD patients at different stages of the …

Radiation-Induced Increases In Pkc Modulate Integrin Expression And Contribute To Fibrotic Changes, Pinal Rushikesh Pandya

Loma Linda University Electronic Theses, Dissertations & Projects

The sequences of events in fibrosis are similar to those in wound healing; however, the normal termination and resolution stages do not take place. The initial cellular response following ionizing radiation involves accumulation of the ECM (extracellular matrix) including collagen, fibronectin and the interaction of many growth factors (cytokines) with their receptors. There are a number of unanswered questions regarding many aspects of radiation-induced fibrosis, including the initial triggers and physical changes that initiate the process. We have confirmed that elevated pKC and other cellular changes following radiation are similar to those found at sites of inflammation. This information leads …

Characterizing Ntrc-Like Activators Affecting Myxococcus Xanthus Development, Jessica Eisenstatt

Honors Capstone Projects - All

Myxococcus xanthus is a soil bacterium that is a member of a group of organisms known as the myxobacteria. M. xanthus cells live in biofilms and feed on other bacteria to obtain nutrients. During times of inadequate nourishment, M. xanthus cells aggregate, build fruiting bodies, and fruiting body cells differentiate into spores that are highly resistant. In order to form the fruiting bodies, M. xanthus cells must be able to move across solid surfaces. There are two motility systems, the adventurous system (A-motility) and the social system (S-motility), used by M. xanthus cells to navigate across surfaces. The adventurous system …

Compensation Mechanisms For Altered Membrane Sterol Compositions In The Yeast: Saccharomyces Cerevisiae, David M. Dewolfe

Honors Capstone Projects - All

Cell Membranes are composed of several different lipid and sterol products. Among these are, chiefly, phospholipids, glycolipids, sphingolipids, various proteins and sterols. The sterol that is prevalent in fungi, including yeast, is ergosterol. It plays the same physiological role as cholesterol in mammalian cells. That is, mainly, to control membrane fluidity. Membranes in general are extremely important to the normal functioning of any cell and its sub-cellular compartments. The primary factor in the normal functioning of a membrane is the relative composition of the previously mentioned components. Even though there is a high amount of traffic between different membranes within …

Characterization Of Hypersensitive Response Related Genes Of Arabidopsis Thaliana, Keluo Yao

Honors Capstone Projects - All

Like most complex living organisms, plants have many mechanisms to prevent disease by microbial pathogens. One of the most important and well developed defense systems that involve recognition, identification and systematic response is the hypersensitive response.

The hypersensitive response is a complex, early defense response against pathogens that causes necrosis and cell death at the site of infection to restrict the spread of pathogen. Hypersensitive response is a type of programmed cell death, and its activation usually happens when the plant recognizes a pathogen through an elicitor. This recognition triggers a series of signal transductions events which end in the …

Characterization Of Type Ii Secretion Mutants Of Pseudomonas Aeruginosa, Sijung Suh

Honors Capstone Projects - All

Pseudomonas aeruginosa mutants PA0686, PA3102, PA3103, and PA5210 carry transposon insertions in uncharacterized genes in the PA01 background. The biofilms formed by these mutants show different phenotypes than PA01, their wild-type counterpart. BLAST searches and phylogenomic mapping tools indicate that protein products of the mutated genes are involved in P. aeruginosa type-II secretion, which is linked to twitching motility. In this study, 96-well microtitre plate biofilm assays, UV/visible spectrophotometer analysis, and motility assays were used to demonstrate a link between type-II secretion, twitching motility and biofilm formation. The results show that the PA5210 mutant forms a biofilm that is less …

Multiplex Snp Discrimination, Daniel J. Fish, M. Todd Horne, Robert P. Searles, Greg P. Brewood, Albert S. Benight

Chemistry Faculty Publications and Presentations

Multiplex hybridization reactions of perfectly matched duplexes and duplexes containing a single basepair mismatch (SNPs) were investigated on DNA microarrays. Effects of duplex length, G-C percentage, and relative position of the SNP on duplex hybridization and SNP resolution were determined. Our theoretical model of multiplex hybridization accurately predicts observed results and implicates target concentration as a critical variable in multiplex SNP detection.

The Effects Of Acute Ethanol Treatment On The Suprachiasmatic Nucleus In Adult Male Mice, Charles Andrew Mangrum

Masters Theses

Light is the primary entraining signal for the mammalian circadian clock located in the suprachiasmatic nucleus (SCN). Light entering the eye leads to release of glutamate directly onto SCN neurons where it binds to N-methyl D-aspartate (NMDA) receptors initiating a cascade of cellular processes that ultimately modulates clock phase. SCN neurons show a 24-hour rhythm in neuronal activity that peaks in the middle of the day when isolated in a brain slice preparation. Treatments that phase-shift the SCN clock in vivo have been shown similarly to shift this rhythm of neuronal activity in vitro. Here, I have investigated …