Digital Commons Network^™

Evidence That A Partner-Switching Regulatory System Modulates Hormogonium Motility In The Filamentous Cyanobacterium Nostoc Punctiforme, Kelsey Wynne Riley

University of the Pacific Theses and Dissertations

Partner-switching regulatory systems (PSRSs) are utilized by many different bacteria to regulate a wide array of cellular responses, from stress response to expression of virulence factors. The filamentous cyanobacterium Nostoc punctiforme can transiently differentiate motile filaments, called hormogonia, in response to various changes in the environment. Hormogonia utilize a Type IV pilus (T4P) complex in conjunction with a secreted polysaccharide for gliding motility along solid surfaces. This study identified three genes, designated hmpU, hmpW, and hmpV, encoding the protein components of a PSRS involved in regulation of hormogonium motility in N. punctiforme. Although mutant strains with in-frame deletions in hmpU, …

Applications Of Low Field Magnetic Resonance Imaging, Muhammad Waqas

University of the Pacific Theses and Dissertations

Magnetic resonance imaging is a non-invasive imaging modality that is used to produce detailed images of soft tissues within the human body. Typically, MRI scanners used in the clinical setting are high field systems because they have a magnetic field strength greater than 1.5 Tesla. The high magnetic field offers the benefit of high spatial resolution and high SNR. However, low filed systems can also produce high resolution MR images with the added benefit of imaging stiffer samples. In this study, a low field 0.5 T MR system was used to image various samples to demonstrate the capability of the …

Rational Design Of Peptides Binding Towards Human Pd-L1 Using Knob-Socket Model, Xingchen Zha

University of the Pacific Theses and Dissertations

Programmed death-ligand 1 (PD-L1) is a type 1 transmembrane protein that has been reported to play a vital role in mediating suppressed immunity. The interaction between PD-L1 and PD-1 delivers a negative signal that reduces the proliferation of these T cells and induces apoptosis at the same time. Antibodies that can block the Programmed death-ligand 1 (PD-L1) on tumor cells have been shown to alleviate cancer-induced immunosuppression. While antibodies have a great potential in various therapeutic uses, many drawbacks such as the high cost of production, huge molecular size, and poor permeability impose restrictions on the extensive use of full-length …

Computational Methods In Biomolecules:Study Of Hydrophilic Interactions In Protein Folding & Constant-Ph Molecular Simulation Of Ph Sensitive Lipid Morc16, Wei Zhang

University of the Pacific Theses and Dissertations

Water molecules play a significant role in biological process and are directly involved with bio-molecules and organic compounds and ions. Recent research has focused on the thermal dynamics and kinetics of water molecules in solution, including experimental (infrared spectroscopy and Raman spectroscopy) and computational (Quantum Mechanics and Molecular Dynamics) approaches. The reason that water molecules are so unique, why they have such a profound influence on bio-activity, why water molecules show some anomalies compared to other small molecules, and where and how water molecules exert their influence on solutes are some of the areas under study. We studied some properties …

Development Of Novel Phenanthroline And Thiazole Orange Derived G-Quadruplex Ligands And Telomerase Inhibitors, Siwen Wang

University of the Pacific Theses and Dissertations

The end of the human chromosome is protected by telomeres which contain a special tandem guanine-rich DNA sequence, 5’-TTAGGG. The length of telomeres is shortened during cell replications, and its length limits the replication capacity of cells. Telomerase is over-expressed in 85–90% of cancer cells, responsible for extending the telomere length in cancer cells. Guanine-rich DNA sequence can self-assemble into unique G-quadruplex structures that interfere with the extension of telomeres by telomerase. Therefore, DNA G-quadruplex has recently received much attention because of its important regulatory functions in telomerase-mediated cancerization. The formation of G-quadruplex requires monovalent cations (Na+ and K+) or …

Should I Stay Or Should I Go? Complex Environments Drive The Developmental Plasticity Of Flight Capacity And Flight-Related Tradeoffs, Jordan R. Glass

University of the Pacific Theses and Dissertations

Animals must balance multiple, fitness-related traits in environments that are complex and characterized by co-varying factors, such as co-variation in temperature and food availability. Thus, experiments manipulating multiple environmental factors provide valuable insight into the role of the environment in shaping not only important traits (e.g., dispersal capacity or reproduction), but also trait-trait interactions (e.g., trade-offs between traits). We employed a multi-factorial design to manipulate variation in temperature (constant 28°C vs. 28±5°C daily cycle) and food availability (unlimited vs. intermittent access) throughout development in the sand field cricket, Gryllus firmus. We found that fitness-related, life-history traits and trait trade-offs can …

Dna Lesions Produced From The Reaction Of Diols And 5-Formylcytosine And Their Effects On Dna Replication, Brock Allen

University of the Pacific Theses and Dissertations

Nucleic acids are complex macromolecules that are susceptible to both endogenous and exogenous damage. This study explored damage resulting from interactions with environmental nucleophilic toxins, such as a variety of diols and amines found in industry. These nucleophiles can react with electrophilic groups, such as 5-formylcytosine. 5-formylcytosine is an oxidation product of the epigenetic base 5-methylcytosine. It is typically removed by thymine DNA glycosylase (TDG) but is known to accumulate in the genome, making the formyl group susceptible to attack. In this study we used GC/MS and ESI-MS to show that DNA lesions from the nucleophilic addition reaction of toxins …

Vector Competence Of Northern California Mosquitoes For Dirofilaria Immitis (Spirurida: Onchocercidae), Rebekah Lynn Dian

University of the Pacific Theses and Dissertations

Dirofilaria immitis, commonly known as dog heartworm, is a dangerous filarial nematode that is transmitted by a mosquito vector. Although this parasite is historically localized to regions closer to the equator, the last few decades have experienced an increase in the amount of dog heartworm cases in Northern California, most notably in Lake and San Joaquin Counties. The primary vector of D. immitis in Northern California is Aedes sierrensis, but it is not prevalent enough in some counties to explain the increase in infections. Because of this, more prevalent and abundant species should be assessed for their ability to transmit …

Aphasia Couples Therapy: A Case Study Of Conversational Coaching For A Man With Conduction Aphasia, Adriana Joma

University of the Pacific Theses and Dissertations

The purpose of this study was to contribute to the understanding of the effects of aphasia couples therapy (ACT) in a person with conduction aphasia. ACT is a social therapeutic approach that involves facilitating conversations between the person with aphasia (PWA) and their spouse, or caregiver. The participants in this study involved one pair. The dependent variables included conveyance of main concepts, use of intentional gestures, reflections and summary statements per conversation. Miscellaneous measures were also counted and analyzed including the PWA’s frequency of paraphasias, fillers (e.g. um, uh), and disfluencies. Baseline sessions involved the PWA watching a video clip, …

Issues Of Equity Among Team Members In Special Education: Voices Of Parents New To Special Education, Amanda R. Johnson

University of the Pacific Theses and Dissertations

The Individuals with Disabilities Education Act requires local education agencies to include parents as equal team members in the cultivation of their child’s individual education plan (IEP). Despite law, studies have shown that parents experience barriers to being included in the process. Barriers such as a lack of information, lack of understanding of the law, and feelings of unequal status or power as compared to school district team members have been noted. The aim of this study was to explore the perceptions, feelings, and understanding of the initial IEP process as experienced by parents new to the world of special …

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 …

Bimetallic Complexes: The Fundamental Aspects Of Metal-Metal Interactions, Ligand Sterics And Application, Michael Bernard Pastor

University of the Pacific Theses and Dissertations

Metal containing complexes have been used to catalyze various organic transformations for the past few decades. The success of several mononuclear catalysts led to transition metal catalysts used in pharmaceuticals, environmental, and industrial processes. While mononuclear complexes have been used extensively, bimetallic systems have received far less attention. Bimetallic or polynuclear sites are commonly found in metalloenzymes that perform elegant transformation in biological systems, underlying their significance. Inorganic chemists take inspiration from nature and design model bimetallic complexes to further study this cooperativity effect. A bimetallic platform offers many structural and functional differences such as the identity of the metal …

Comparing Equivalence-Based Instruction With Lecture-Based Instruction To Teach College Students To Identify Logical Fallacies, Kelly Roughgarden

University of the Pacific Theses and Dissertations

Educators and practicing professionals in many fields emphasize the importance of critical thinking for effective decision-making. However, critical thinking skills are not usually directly taught in traditional educational settings. A subset of these skills, identifying logical fallacies, could be amenable to direct instruction using procedures that establish conditional discriminations, such as equivalence-based instruction (EBI). EBI procedures have been shown to be effective and efficient when teaching a variety of skills, including the identification of logical fallacies, when compared with no-instruction and self-instruction control groups. The purpose of this study is to compare the effectiveness of web-based EBI procedures to a …

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 …

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 …

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 …

Control Of Pancreatic Β-Cell Bioenergetics., Charles Affourtit, Ben Alberts, Jonathan Barlow, Je Carré, Anthony G. Wynne

School of Biomedical Sciences

The canonical model of glucose-stimulated insulin secretion (GSIS) by pancreatic β-cells predicts a glucose-induced rise in the cytosolic ATP/ADP ratio. Such bioenergetic sensitivity to metabolic fuel is unusual as it implies that ATP flux is governed, to a significant extent, by ATP supply, while it is predominantly demand-driven in other cell types. Metabolic control is generally shared between different processes, but potential control of ATP consumption over β-cell bioenergetics has been largely ignored to date. The present paper offers a brief overview of experimental evidence that demonstrates ATP flux control by glucose-fuelled oxidative phosphorylation. Based on old and new data, …

A New Use Of Β-Ala-Lys (Amca) As A Transport Reporter For Pept1 And Pept2 In Renal Brush Border Membrane Vesicles From The Outer Cortex And Outer Medulla., Othman A. Alghamdi, Nicola King, Graham L. Jones, Pierre D.J. Moens

School of Biomedical Sciences

Integral membrane proteins PEPT1 and PEPT2 are essential for reabsorbing almost all hydrolysed or filtered di- and tripeptides alongside a wide range of peptidomimetic drugs in the kidney. The aim of this study was to investigate the potential use of the fluorophore-conjugated dipeptide β-Ala-Lys (AMCA) as a biosensor for measuring peptide transport activity in brush border membrane vesicles isolated from the outer cortex (BBMV-OC) and outer medulla (BBMV-OM) (representing PEPT1 and PEPT2 respectively). The vesicles were isolated using a dual magnesium precipitation and centrifugation technique. Intravesicular fluorescence accumulation was measured after incubating extra-vesicular media at pH6.6 and different concentrations of …

Prevention Of Tuberculosis In Rhesus Macaques By A Cytomegalovirus-Based Vaccine, Scott G. Hansen, Daniel E. Zak, Guangwu Xu, Julia C. Ford, Emily E. Marshall, Daniel Malouli, Roxanne M. Gilbride, Colette M. Hughes, Abigail B. Ventura, Emily Ainslie, Kurt T. Randall, Andrea N. Selseth, Parker Rundstrom, Lauren Herlache, Matthew S. Lewis, Haesun Park, Shannon L. Planer, John M. Turner, Miranda Fischer, Christina Armstrong, Robert C. Zweig, Joseph Valvo, Jackie M. Braun, Smitha Shankar, Lenette Lu, Andrew W. Sylwester, Alfred W. Legasse, Martin Messerle, Michael A. Jarvis, Michael A. Jarvis, Alan Aderem, Galit Alter, Dominick J. Laddy, Michele Stone, Aurelio Bonavia, Thomas G. Evans, Michael K. Axthelm, K Fruh, Paul T. Edlefsen, Louis J. Picker

School of Biomedical Sciences

No abstract provided.

Parallel Genome-Wide Profiling Of Coding And Non-Coding Rnas To Identify Novel Regulatory Elements In Embryonic And Maturated Heart, Davood Sabour, Rui S.R. Machado, José P. Pinto, Susan Rohani, Raja G.A. Sahito, Jürgen Hescheler, Matthias E. Futschik, Agapios Sachinidis

School of Biomedical Sciences

No abstract provided.

Effect Of Exercise Therapy On Established And Emerging Circulating Biomarkers In Patients With Heart Failure: A Systematic Review And Meta-Analysis, Melissa J. Pearson, Nicola King, Neil A. Smart

School of Biomedical Sciences

No abstract provided.

Foxn1-Dependent Thymic Epithelial Cells Promote T-Cell Leukemia Development, Marinella N. Ghezzo, Mónica T. Fernandes, Ivette Pacheco-Leyva, Pedro M. Rodrigues, Rui S. Machado, Mas Araujo, Ravi K. Kalathur, Matthias E. Futschik, Nuno L. Alves, Santos Nr Dos

School of Biomedical Sciences

No abstract provided.

Cd44 Is Required For The Pathogenesis Of Experimental Crescentic Glomerulonephritis And Collapsing Focal Segmental Glomerulosclerosis, Jennifer Eymael, S Sharma, Markus A. Loeven, Jack F. Wetzels, Fieke Mooren, Sandrine Florquin, Jeroen K. Deegens, Brigith K. Willemsen, V Sharma, Kuppevelt Th Van, Marinka A. Bakker, Tammo Ostendorf, Marcus J. Moeller, Henry B. Dijkman, Bart Smeets, Der Vlag J Van

School of Biomedical Sciences

© 2017 International Society of Nephrology. A key feature of glomerular diseases such as crescentic glomerulonephritis and focal segmental glomerulosclerosis is the activation, migration and proliferation of parietal epithelial cells. CD44-positive activated parietal epithelial cells have been identified in proliferative cellular lesions in glomerular disease. However, it remains unknown whether CD44-positive parietal epithelial cells contribute to the pathogenesis of scarring glomerular diseases. Here, we evaluated this in experimental crescentic glomerulonephritis and the transgenic anti-Thy1.1 model for collapsing focal segmental glomerulosclerosis in CD44-deficient (cd44-/-) and wild type mice. For both models albuminuria was significantly lower in cd44-/- compared to wild type …