Life Sciences Commons^™

Investigating Bzip Recognition Of Dna Sequences Through A Knob-Socket Perspective, Aaron Tran

University of the Pacific Theses and Dissertations

To investigate whether higher order packing interactions confer protein-DNA specificity, a modified Knob-Socket (KS) model was used to analyze the interface of bZIP-DNA crystal structures. The KS analysis identified a nine-residue quadripartite recognition core consisting of four contiguous KS pockets P1, P2, N3, and N4 that each pack one of the four DNA half-site bases in the target sequence. Only one base per base pair packs, and these interactions are split across the DNA strands: the first two positive strand positions 1p and 2p pack into P1 and P2 while the last two negative strand positions 3n and 4n pack …

Optimizing The Human Aryl Hydrocarbon Receptor (Hahr) Expression In Pichia Pastoris, Junyu Qian

University of the Pacific Theses and Dissertations

The aryl hydrocarbon receptor (AHR) is a transcription factor which heterodimerizes with the aryl hydrocarbon receptor nuclear translocator (Arnt) to regulate downstream gene transcription. For the purpose of studying the crystal structure of human aryl hydrocarbon receptor (hAHR), it is essential to obtain abundant amount of pure recombinant protein.Basing on the benefits of using P. pastoris system to produce recombinant protein, including appropriate folding, secretion of interest proteins to the external environment of the cell, and easier purification process of protein due to the its limited production of endogenous secretory proteins [1], our lab chose P. pastoris yeast as the …

The Interrelationship Between Treatment, Ethnicity, And Structured Exercise In Clinical Populations, Amanda M. F. Lopez

University of the Pacific Theses and Dissertations

Cancer is the second leading cause of death, with about approximately 1.9 million Americans being diagnosed each year. Yet, it has high survival rates with the help of advancing treatments like radiation therapy. Cancer patients and survivors are contingent on experiencing a decline in physical functioning, quality of life, and physiological parameters. Treatment is effective and can prolong life expectancy but can be deleterious to a patient’s health. Parallel with cancer's impact on Americans is cardiovascular disease. Cardiovascular disease is responsible for 1 in 4 deaths. The development of cardiovascular disease is not spread accordantly among all ethnicities. Hispanics are …

Post-Translational Modification And Degradation Mechanisms Of The Aryl Hydrocarbon Receptor, Yujie Yang

University of the Pacific Theses and Dissertations

The aryl hydrocarbon receptor (AHR) is a transcription factor first discovered to be activated by exogenous ligands, such as dioxins, and helps promote downstream gene (e.g. CYP1A1) transcription to metabolize the toxicants. With the reports of various AHR targets genes, the expression levels and activities of AHR have been implicated in many physiological and pathological situations. Understanding how AHR protein level is regulated would provide more information to target AHR. AHR stays in the cytosol in the absence of ligand in a complex with HSP90, p23 and XAP2. After ligand activation, AHR translocates into the nucleus, fulfilling its transactivation function …

Development Of Linked-Domain Protein Inhibitors Of The E2-Conjugating Enzyme Ube2d, Anneroos E. Nederstigt

University of the Pacific Theses and Dissertations

In most eukaryotic organisms, the ubiquitination pathway is one of the most important and versatile signaling systems in use. It is integral to processes such as protein degradation and homeostasis, DNA repair cell cycle regulation, signaling and regulation, epigenetics, and many more. Ubiquitin (Ub) is a short polypeptide of 8.6 kDa, 76 residues that functions as a reversible post-translation modification (PTM). It furthermore contains 7 different lysine residues (K6, K11, K27, K29, K33, K48, K63), all of which can form isopeptide linkages with one another to link individual Ub moieties to form unique polyUb chains onto substrates. The type of …

Knob-Socket Investigation Of Stability And Specificity In Alpha-Helical Secondary And Quaternary Packing Structure, Taylor Renee Rabara

University of the Pacific Theses and Dissertations

The novel knob-socket (KS) model provides a construct to interpret and analyze the direct contributions of amino acid residues to the stability in α-helical protein structures. Based on residue preferences derived from a set of protein structures, the KS construct characterizes intra- and inter-helical packing into regular patterns of simple motifs. The KS model was used in the de novo design of an α-helical homodimer, KSα1.1. Using site-directed mutagenesis, KSα1.1 point mutants were designed to selectively increase and decrease stability by relating KS propensities with changes to α-helical structure. This study suggests that the sockets from the KS Model can …

Investigating The Effect Of Rutaecarpine On The Benzo[A]Pyrene-Induced Dna Damage In Vitro, You Li

University of the Pacific Theses and Dissertations

Benzo[a]pyrene (BaP), is one of the most potent mutagens and carcinogens known. It requires metabolic activation through cytochrome P450 (CYP)1A1 to yield the ultimate carcinogenic metabolite, benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE). BPDE can bind to DNA and form predominantly covalent (+) trans adducts at the N2 position of guanine causing DNA damage. Rutaecarpine (RTC) is an herbal medicine that has been used to treat several diseases such as headache, hypertension, gastrointestinal disorders, amenorrhea, and anti-inflammation. It has also been reported as a potent inducer of CYP enzymes, including CYP1A1, and CYP1A2. The mechanisms underlying up-regulation of CYP1A1 by RTC is dependent on aryl …

Design And In Vitro Characterization Of Lipids With A Ph-Sensitive Conformational Switch And Their Liposomes For Anticancer Drug Delivery, Shen Zhao

University of the Pacific Theses and Dissertations

The traditional anticancer drugs are distributed in vivo through systemic blood circulation with a very small portion reaching the tumor site. Targeted drug delivery systems are developed in efforts to concentrate the drug molecules in the tissue of interest while reducing the drug distribution to healthy tissues to reduce the side effects. Liposomes are colloidal systems composed of amphiphilic molecules that assemble into vesicle structures in aqueous media. They are common carriers for targeted drug delivery with the advantages of low toxicity, low immunogenicity and the ability of encapsulating both lipophilic and hydrophilic drugs.

Prior research indicated the advantages of …

Influence Of The Estrous Cycle And Female Sex Hormones On Ghb Toxicokinetics, Hao Wei

University of the Pacific Theses and Dissertations

Gamma-Hydroxybutyrate (GHB) is an endogenous short-chain fatty acid formed from Gamma-aminobutyric acid (GABA). Clinically, GHB is marketed in the United States as Xyrem to treat narcolepsy with cataplexy and in Europe for the treatment of alcohol withdrawal and narcolepsy. However, the illicit use and abuse of GHB occurs due to its sedative/hypnotic and euphoric effects. Monocarboxylate transporters (MCTs and SMCTs) are integral membrane proteins that control the bidirectional transport of endogenous substrates including lactate, acetate and pyruvate. They have also been found to transport and mediate the clearance and distribution of GHB. MCTs demonstrate a wide tissue distribution, including brain, …

Peptide-Drug Conjugate For Her2-Targeted Drug Delivery, Yan Wang

University of the Pacific Theses and Dissertations

Recent strategies for anticancer drug design have been focused on utilizing antibody as a drug or targeted moiety for targeted drug delivery. Antibody−drug conjugates (ADCs) have become a promising new class of targeted therapeutic agents for treatment of cancer. ADCs are designed to preferentially direct a cytotoxic drug to a cell-surface antigen recognized by an antibody. However, there are some challenges in developing ADCs, such as limited solid tumor penetration, high manufacturing costs and antibody-drug stoichiometry. Smaller molecules such as peptides have been shown to specifically bind to cancer related targets. These peptides can be used to form peptide-drug conjugates …

Investigations On Cancer Cell Biological Effects Of Cdk8 Inhibitor Q-12, Zhixin Lu

University of the Pacific Theses and Dissertations

Over the past two decades, protein kinases have been intensively investigated as targets to treat neoplastic diseases. Many protein kinase inhibitors not only have therapeutic potential but are becoming invaluable reagents for the study of cell signaling.

We aspired to use our Cyclin-Dependent Kinase 8 inhibitor, Q-12, as a probe for biomarker discovery for CDK8 inhibitor sensitive tumor types. Q-12 shows potent inhibition of cell viability and induction of apoptosis process in some triple-negative breast cancer and colorectal cancer cell lines in vitro. Western blot results indicate that the reduction of STAT1 phosphorylation could be a robust indicator of CDK8 …

Determining The Role Played By Aryl Hydrocarbon Receptor (Ahr) In The Colon Carcinoma Tumor Model, Poonam Yakkundi

University of the Pacific Theses and Dissertations

Aryl hydrocarbon receptor (AHR), commonly known as an environmental sensor involved in the metabolism and elimination of xenobiotic substances, is also an important modulator in the development and functioning of the immune system. AHR expression is varied in the T cell subsets with the highest expression in T-helper 17 and T regulatory cells. Work from many researchers has suggested that AHR can act as a tumor promoter or a tumor suppressor depending on the tumor type. Our goal is to understand the role played by AHR in MC38 syngeneic colon carcinoma tumor model. In the absence of AHR, MC38 tumor …

Comparison Of Zeocin And G418 Resistance Markers In Pichia Pastoris, Allison Moy

University of the Pacific Theses and Dissertations

The methylotrophic yeast, Pichia pastoris, has been used to successfully produce and express over 700 heterologous proteins. Currently, the only two dominant selectable markers available are the Zeocin and blasticidin resistance genes. This study focused on characterizing and developing the modified G418 selectable marker so it could be used for primary selection of single copy and multicopy strains. To demonstrate its use as a selectable marker the SLPI reporter gene was inserted into the Zeocin resistance vector, pPICZB, and the new G418 resistance vector, pKANa B. The resulting constructs were then transformed into P. pastoris yJC100 cells. Piggyback strains containing …

Optimization Of Porcine Buccal Mucosa For In Vitro Evaluation, Upendra D. Kulkarni

University of the Pacific Theses and Dissertations

Porcine buccal mucosa has been extensively used as in vitro model to study the permeability of drugs and assess their potential to deliver through buccal route. Porcine buccal mucosa is found to be very similar to human oral mucosa in structure and function. However, the in vitro permeation studies across porcine buccal mucosa show high variability which is mostly due to the various experimental and biological variables that are often overlooked while conducting such studies.

The precise nature of the permeability barrier offered by the various tissue layers of buccal mucosa was investigated in this study. It was observed that …

High Pressure Liquid Chromatography Ion Exchange Studies On Bile Relating To The Postmortem Interval, Bertha Louise Martin

University of the Pacific Theses and Dissertations

It is the purpose of this, then, to investigate the feasibility of using the changes of concentrations of small iconic decomposition products in bile as indicators of time since death. High pressure liquid chromatography was selected for measurement of these changes.

The Effect Of A Balanced Amino Acid Infusion On Hepatic Regeneration In Rats, Robert Arthur Anstadt

University of the Pacific Theses and Dissertations

The efficacy of a balanced amino acid infusion on recovery from temporary hepatic insufficiency and its effect on plasma ammonia levels in partially hepatectomized rats were studied.

Polyethylene implant buttons were developed to secure animals to the infusion apparatus. Rats under went jugular vein cannulation, and 70% partial hepatectomy. Test solutions were continuously infused (30 ml/d). Plasma samples were taken through the jugular vein cannula and analyzed for bilirubin concentration, ammonia concentration, LDH activity, and GPT activity.

LDH and bilirubin results were inconclusive. Results from GPT activity assays suggest that both Freamine III and the balanced formula provided injured hepatocytes …

The Partial Purification And Characterization Of A Soluble Activator For The Sodium Adenosinetriphosphatase From Rat Cerebral Cortex And The Effect Of Cholinergic Agents, Thibaldo Javier Manrique Blanco

University of the Pacific Theses and Dissertations

In order for organisms to co-exist with nonliving matter, envelop to protect their delicate internal functions must be present. There are other reasons for this boundary to exist, e.g. to limit the volume occupied by the organism and to compartmentalize the contents of the organism so that certain critical concentrations may be easily maintained. Such envelopes are, of course, the cellular membranes. Membranes differ greatly between species, as well as within species. Given the complexity to which organisms have evolved, membranes have developed with a myriad of functions and components. It is easy to see differences between plant cellular membranes …

The Effects Of Health Related Feedback On A Smoking Cessation Maintenance Program, Janice A. Blalock

University of the Pacific Theses and Dissertations

The present study investigated the effectiveness of health related feedback as a positive reinforcer of abstinence from smoking during the 11 week period following cessation. Fifty-three subjects were randomly assigned to one of three groups: (a) maintenance program plus health related feedback (MF), (b) maintenance program only (M) and, (c) discussion control (D). All groups received an aversive treatment for smoking after which the MP group received coping skills raining and several forms of health related feedback, the M group received coping skills training only, and the D group received discussion. Groups did not differ significantly in abstinence at each …

Pharmacognosy Of The Saururaceae : Microscopy Of Powdered Drugs, Prakash Vaman Mallya

University of the Pacific Theses and Dissertations

Plants of the family Sauruaceae are used in folk medicine in various parts of the world. Chemistry of some plants of this family and their chemotaxonomy has been investigated in our laboratory (12).

It is very difficult to establish identity and authenticity of commercially available crude drugs and powders of the Saururaceae because a detailed, collective study of microscopic features of these plants is not available. Original papers establishing plants of this family (see later) do not include microscopic features; they describe only gross morphologic and other classical features required for systematics. They are not useful for a pharmacologist in …

The Synthesis Of Various Substituted 3-Amino-7-Hydroxy-2,2-Dimethyltetralins And Their Opioid-Related Activities, David Alan Lippman

University of the Pacific Theses and Dissertations

A series of aminotetralones and aminotetralins were synthesized from the common intermediate F, 3-amino-2,2-dimethyl-7-methoxy- 1-tetralone. The final compounds derived from F were simple substituted and/or reduced analogues. The products would allow a progressive structure activity relationship to be drawn based on pharmacological testing.

The common intermediate F was synthesized utilizing a six step procedure starting with p-methoxyphenylacetic acid. The overall yield from the precursor to the F:HC1 was 25%. Compound F was either O-demethylated to form 3-amino-2,2-dimethyl-7-hydroxy-l-tetralone (I) or was dimethylated on the amine and subsequently O-demethylated to yield the 3-dimethylamino-7-hydroxy-2,2-dimethyl-l-tetralone (J). The last major modification was the reduction of …

Computerized Formulation And Optimization Of Medicated Chewing Gum, Daniel J. Berky

University of the Pacific Theses and Dissertations

Sixty Four caffeinated chewing gum preparations were formulated by varying the amounts of (i) cinnamaldhyde, (0-0.75%), (ii) docusate (0-0.5%) and (iii) sucrose (40-60%). The gum base consisted of 33.33% yellow beeswax and 66.66% polyisobutylene MH, and was added, adjusting for a final weight of 2 grams per gum. The amount of caffeine was maintained at 100mg. The preparations were subjected to an in vivo release study as well as a hedonic survey with a panel of student volunteers.

Data were analyzed by using multiple linear regression on a mainframe computer. The resulting mathematical model was used to predict a theoretically …

Enteric Infections In Stockton, California : With Special Reference To The Genus Campylobacter, Tom Edward Hathorn

University of the Pacific Theses and Dissertations

During the last two or three years, the three largest hospitals in Stockton (St. Joseph’s, Dameron and San Joaquin General Hospitals) have modified their procedures to include the search for Campylobacter. On the other hand, the incidence of Yersinia in California is unknown, as most clinical laboratories do not specifically culture for it. There have been only a few reports of Yersinia in this state (personal communication of Dennis Ferrero, Director of the San Joaquin County Public Health Laboratory). This study has a threefold purpose: to investigate the incidences of Campylobacter and Yersinia, especially in relation to the incidence of …

The Effect Of Heparin On Growth Characteristics Of Transplanted Spontaneously Occurring C3h/Hej Mouse Mammary Tumor, Muhammed Saleh Abdullah Banaja

University of the Pacific Theses and Dissertations

Mouse mammary tumor is a common form of cancer used for experimental purposes. It is relatively resistant to chemotherapy. This investigation is designed to test the effect of heparin, a naturally occurring anticoagulant, on tumor growth using a genetically uniform laboratory animal.

Protective Effects Of Certain Lythraceae Alkaloids And Homologs In Croton Oil- And Carrageenan-Induced Inflammation, John Alan Byrne

University of the Pacific Theses and Dissertations

Cryogenine's immunosuppressive activity was first evaluated by Kosersky, et al. (21) who, impressed by the drug's ability to inhibit both the irritant- and immune- mediated phases of adjuvant-induced polyarthritis (11), quantitatively confirmed this activity and clearly differentiated the action of cryogenine from that displayed by 6-mercaptopurine. A definitive study by Watson and Malone (22) confirmed cryogenine's lack of immunosuppressive capacity at effective anti-inflammatory dose levels.

The molecular complexity of the lythraceae alkaloids suggests that several active centers may account for their unique pharmacological profile. To assess these potentially active sites, two standard models of acute inflammation were selected for use …

Effects Of Fixed Interval And Continuous Biofeedback Reinforcement On Emg Frontalis Muscle Activity, Kathleen I. Twinem

University of the Pacific Theses and Dissertations

The effects of continuous vs. intermittent reinforcement using electromyographic (EMG) feedback as the reinforcer were compared in reducing frontalis muscle activity. Fourteen subjects were chosen from a group of 30 students who had expressed an interest in learning how to relax. Those students having the highest pre-experimental baseline scores were chosen. They were matched according to both those scores and sex and then randomly assigned to either a continuous biofeedback reinforcement group or a 30 sec. fixed interval biofeedback reinforcement group. The experiment consisted of nine sessions (three acquisition, two treatment, and four extinction) with integrated EMG activity from the …

Alterations Of Central Dopamine Receptor Sensitivity In The Spontaneously Hypertensive Rat, John Richard Martin

University of the Pacific Theses and Dissertations

Since the time of the introduction of the spontaneously hypertensive rat (SHR) into medical research, several neuropharmacological studies have been performed on these animals which have been unrelated to their cardiovascular systems. A few of these studies have indicated possible abnormalities in the dopaminergic systems of SHR. Therefore the present study was undertaken to examine more closely the sensitivity of SHR to stimulation of their dopamine (DA) receptors.

An Epidemiological Study Of Human Toxoplasmosis In San Joaquin County, California, Peter Lund

University of the Pacific Theses and Dissertations

The major purpose of this study was to correlate certain personal characteristics of mothers and their offspring with the occurrence of toxoplasmosis serum antibodies in these women. As a byproduct, we determined the prevalence and incidence of toxoplasmosis in a particular subgroup of women in the Stockton, California area of San Joaquin County.

We had also hoped to provide early diagnostic services and follow up for any infected infants that we encountered. Unfortunately, follow up on these infants has been difficult largely due to the migrant habits of this particular group of seasonal farm workers. For these reasons this study …

A Biosystematic Investigation Of Medically Important Yeasts, Nancy Christiansen Ballot

University of the Pacific Theses and Dissertations

The purpose of this study is twofold: (1) conduct an epidemiological survey of yeasts found in clinical material; and (2) suggest an identification scheme that would identify yeasts of medical importance in the shortest possible time.

The Biochemistry Of Vascular Smooth Muscle In The Spontaneously Hypertensive Rat, John Edward Taylor

University of the Pacific Theses and Dissertations

Cyclic adenosine 3’,5’-monophosphate (cAMP) was first described as the mediator of the glycogenolytic effect of epinephrine and glucagon in the liver almost two decades ago. It has since been found that cAMP may mediate the effects of a number of hormones and neurohormones, and this observation has led to the development of the second messenger hypothesis of hormone action. According to the second messenger theory, the hormone or first messenger brings information to the cell, whereas, the second messenger (cAMP) transfers this information into intracellular events. More recent evidence has described the existence of an additional second messenger, cyclic guanosine …

The Use Of Habit Reversal In Reducing Tics With Two Institutionalized Individuals, Phyllis Williamson

University of the Pacific Theses and Dissertations

The possible application of habit reversal to mentally ill institutional residents has not been investigated. While habit reversal holds considerable promise as a treatment mode, due to its rapid success and patient involvement in controlling his-her own behavior, further research is in order. To investigate the generality of habit reversal to an institutionalized population, the present study utilized self-monitoring, which has been found to be effective with hospitalized patients, and habit reversal, which has been found to be effective with a non-hospitalized population, as a treatment package for eliminating nervous tics. There are four major purposes for doing this present …