Life Sciences Commons^™

Analyzing Functional Interactions Of Designed Peptides By Nmr Spectroscopy, Wonsuk Choi

Pharmaceutical Sciences (MS) Theses

The development of small peptide-based therapeutics can be accelerated by the knowledge of relationships between the peptide structure and its functional interactions. Here, we report the analysis of two groups of synthetic peptides designed for two applications – broad bactericidal action and inhibition of protein-protein interactions in human cells. Novel amphiphilic peptides designed for antibacterial application incorporated arginine as cationic amino acids and non-natural amino acids that have aromatic side chains with similar hydrophobic properties as tryptophan. The interaction of lead cyclic peptides and their linear analogs with a phospholipid bilayer mimicking a bacterial membrane was studied using nuclear magnetic …

Computational Molecular Docking Studies Of Small Molecule Inhibitors With The Sars-Cov-2 Spike Protein Variants: In-Silico Drug Discovery Using Virtual Screening And Drug Repurposing Approaches, Grace Gupta

Computational and Data Sciences (MS) Theses

The pandemic caused by the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 has caused a global public health crisis of nearly unprecedented scale. In the years following the outbreak, the scientific community has mobilized to develop several vaccines and treatments. Drug repurposing as a strategy for drug development has produced many of the current therapeutic options. The greatest challenge to designing a therapeutic inhibitor of SARS-CoV-2 is the shifting mutational landscape of the virus as it evolves. In this study, we focus on the spike protein as a target for potential inhibitors. We explore two …

Computational Analysis Of Antibody Binding Mechanisms To The Omicron Rbd Of Sars-Cov-2 Spike Protein: Identification Of Epitopes And Hotspots For Developing Effective Therapeutic Strategies, Mohammed Alshahrani

Computational and Data Sciences (PhD) Dissertations

The advent of the Omicron strain of SARS-CoV-2 has elicited apprehension regarding its potential influence on the effectiveness of current vaccines and antibody treatments. The present investigation involved the implementation of mutational scanning analyses to examine the impact of Omicron mutations on the binding affinity of four categories of antibodies that target the Omicron receptor binding domain (RBD) of the Spike protein. The study demonstrates that the Omicron variant harbors 23 unique mutations across the RBD regions I, II, III, and IV. Of these mutations, seven are shared between RBD regions I and II, while three are shared among RBD …

Kinetic And Mass Spectrometric Characterization Of Anti-Greening Mechanisms Of Cysteine And Glutathione In Chlorogenic Acid-Lysine Solutions, Charles Taylor Drucker

Food Science (MS) Theses

Effective decolorization methods mitigating green compound formation from alkaline chlorogenic acid-amino acid reactions can facilitate greater consumption of chlorogenic acid-rich products. While thiols show promise as decolorization agents to replace sulfites, their application has not been optimized. In this work, cysteine and glutathione were probed for their varying kinetic effects on the onset of chlorogenic acid-lysine induced greening. A six-parameter model developed from a reparametrized Weibull cumulative distribution function accurately captured the time- and thiol concentration-dependence of greening in chlorogenic acid-lysine-thiol solutions at pH 8.0 and 9.0, illustrating the pH-dependence of each thiol’s effectiveness at lowering terminal greening magnitude as …

Identifying A Glucocorticoid-Activated Gpcr That Rapidly And Non-Genomically Increases Camp Levels In Mammalian Cells, Francisco Nunez

Pharmaceutical Sciences (PhD) Dissertations

Glucocorticoids (GCs) are steroid hormones that regulate diverse physiological processes. Synthetic versions of GCs are commonly used to treat inflammatory diseases such as asthma by modulating gene expression to suppressing several inflammatory activities. However, it is estimated that 5-10% of asthmatics are unresponsive to GCs, which may be explained by receptor desensitization and/or the presence of a neutrophilic endotype. One understudied phenomenon of GCs is their ability to induce rapid, non-genomic actions. For example, GCs can acutely modulate calcium concentrations levels, induce smooth muscle relaxation and modulate nitric oxide synthase activity, within minutes and sometimes seconds, which is too rapid …

Microbiological Safety And Quality Of Raw, Ready-To-Eat (Rte) Seafood Sold In Orange County, California, Grace Marquis

Food Science (MS) Theses

Raw, ready-to-eat (RTE) seafood can pose health threats due to the potential presence of foodborne pathogens. Listeria monocytogenes is a known microbiological hazard associated with raw, RTE seafood. Salmonella enterica has not traditionally been recognized as a hazard in seafood, but it is an emerging concern, with five outbreaks in seafood in the United States from 2011 to 2021. The presence of E. coli and total coliforms can indicate fecal or environmental contamination. The objective of this study was to evaluate the microbiological safety and quality of raw, RTE seafood sold in Orange County, CA. A total of 105 raw, …

Characterization Of Gangliosides And Fatty Acids In Extracellular Vesicles From Human Milk, Aliya Amin

Food Science (MS) Theses

Extracellular vesicles (EVs) are bioactive components of human milk that may impact functionality to regulate growth, cognitive development, metabolism, and immunity in newborns. The biogenesis of EVs and the mechanism by which EVs elicit biologic effects in vivo have not been characterized entirely. Gangliosides and fatty acids are integral in the formation, release, stability, and functionalities of EVs. Presumably, EV function is related to EV composition and lipids in EVs influence the bioavailability of EV cargo and downstream functions of EVs. The objective of this research was to characterize the fatty acid and ganglioside composition of EVs in human milk. …

Kshv Susceptibility And Transmission Within Tonsillar Specimens, Farizeh Aalam

Pharmaceutical Sciences (PhD) Dissertations

Despite nearly three decades of research, not much is known regarding the early stages of development for KSHV lymphoproliferative disorders, hindering our ability to develop prophylactic measures or effective treatments. This dissertation will focus on the host and viral factors influencing the magnitude and dynamics of KSHV infection in the human tonsil to pave the way for future interventions directed at limiting person-to-person transmission of KSHV.

To understand the contribution of host factors to KSHV susceptibility in B lymphocytes, we generated a library of 40 tonsillar specimens. Our results indicate that the immunological composition of tonsillar lymphocytes varies across our …

Gamma And X-Ray Irradiation Improve Postharvest Shelf-Life In 'Bartlett' Pears, Matthew Garcia

Food Science (MS) Theses

The objective of this study was to investigate the effects of gamma and x-ray treatment on ‘Bartlett’ pear physiology during postharvest storage. Freshly harvested ‘Bartlett’ pears were irradiated with gamma irradiation at 0.412 and 0.819 kGy and x-ray irradiation at 1.03 and 1.94 kGy, then stored at 0-1 ⁰C and 95% relative humidity. The pears were removed from cold storage at 45 and 75 days and allowed to ripen at room temperature for four and two days, respectively. Respiration rate and ethylene production were measured during fruit ripening. Color, firmness, titratable acidity, soluble solids contents, and occurrence of superficial scald …

Characterization Of The Growth Factor Receptor Network Oncogenes In Lung Cancer, Ashley Duche

Pharmaceutical Sciences (MS) Theses

Lung cancer remains the leading cause of cancer related deaths worldwide, reportedly contributing to 1.8 million of the 10.0 million mortalities documented in the year 2020. Although advancements have been made in therapeutics and diagnostic methods, formulation of effective treatments and development of drug resistance continues to be a challenge. These challenges arise from our lack of understanding of intricate signaling pathways, such as the Growth Factor Receptor Network (GFRN), which contributes to complex lung tumor heterogeneity allowing for drug resistance development. In this study, gene expression signatures of six GFRN oncogenes overexpressed in human mammary epithelial cells (HMECs) were …

Automated Parsing Of Flexible Molecular Systems Using Principal Component Analysis And K-Means Clustering Techniques, Matthew J. Nwerem

Computational and Data Sciences (MS) Theses

Computational investigation of molecular structures and reactions of biological and pharmaceutical interests remains a grand scientific challenge due to the size and conformational flexibility of these systems. The work requires parsing and analyzing thousands of conformations in each molecular state for meaningful chemical information and subjecting the ensemble to costly quantum chemical calculations. The current status quo typically involves a manual process where the investigator must look at each conformation, separating each into structural families. This process is time-intensive and tedious, making this process infeasible in some cases, and limiting the ability of theoreticians to study these systems. However, the …

Application Of A Dna Mini-Barcoding System Based On The Mitochondrial Control Region For The Identification Of Raw And Processed Tuna Products, Jiahleen Roungchun

Food Science (MS) Theses

Accurate species identification methods are needed to combat tuna fraud, improve tuna stock regulation, and mitigate health risks associated with mislabeled tuna products. The objective of this study was to conduct a market survey of raw and processed tuna products using a DNA mini-barcoding system based on the mitochondrial control region (CR). A total of 80 samples of raw, dried, and canned tuna products were collected at the retail level for CR mini-barcoding analysis. The samples underwent DNA extraction, polymerase chain reaction (PCR), and DNA sequencing of the 236-bp CR mini-barcode. The resulting sequences were searched against GenBank using the …

Assessing The Efficacy Of Bacteriological Analytical Manual (Bam) Enrichment Broths For Detection Of Salmonella Spp. In Meat Analogs, Georgia Sampson

Food Science (MS) Theses

Plant-based meat alternatives are gaining popularity as the number of market options increases. However, the recent appearance of these products on the market post-dates the validation of the current approach for isolating Salmonella from meat analogs. Therefore, the objective of this study was to compare the efficacy of the currently used Bacteriological Analytical Manual (BAM) pre-enrichment broth (lactose broth) with two additional broths (universal pre-enrichment broth and buffered peptone water) for the detection of Salmonella in five plant-based burger products. Each burger product was spiked with a Salmonella serotype (S. Enteritidis or S. Agona) that has previously been linked …

The Impact Of Processing On The Content And Composition Of Bovine Milk Extracellular Vesicles, Anna Colella

Food Science (MS) Theses

Bovine milk (BM)-based formula is an alternative for many newborns who do not consume human milk. BM contains extracellular vesicles (EVs), bioactive compounds involved in intercellular communication which regulate critical developmental processes in early life. It was hypothesized that the industrial processing of raw BM affected the content and composition of BM EVs. It is critical to understand how industrial processing affects EVs in BM since changes in the content and composition may attenuate the functions of these bioactive compounds in human health. EVs from raw BM were isolated and characterized in accordance with the Minimal Information for Studies of …

Drug Repurposing For Covid-19 Using Molecular Docking Tools, Deniz Yasar Oztas

Computational and Data Sciences (MS) Theses

Since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly contagious and mortal, finding a treatment is time critical. Drug repurposing is probably the quickest and safest approach in our arsenal. However, testing every drug in a brute force manner would require a lot of resources, and a more sophisticated method is required to filter possible candidates. Since several molecules have already been shown to be effective against SARS-CoV-2 in wet-lab experiments, choosing drugs with similar characteristics would increase our chances of success. In this study, we compare the molecular docking results of FDA-approved drugs from the ZINC database against …

Pathogenesis Of Dry Eye In Graft Versus Host Disease (Gvhd): Role Of Ocular Mucins And Conjunctival Fibrosis, Kiumars Shamloo

Pharmaceutical Sciences (PhD) Dissertations

Allogenic hematopoietic stem cell transplantation is a procedure that offers a possible cure for hematologic cancers and other hematologic disorders. Unfortunately, despite the increasing survival rate of patients, the quality of their life is adversely affected by the allogeneic bone marrow transplantation’s major side effect i.e Graft vs. Host Disease (GVHD). GVHD is a complex, multi-organ disease resulting from an immunological attack by donor engrafted immune cells to host organs, including the eye surface. Mostly based on the time of disease onset after transplantation, GVHD is divided into the acute and chronic phase. The eyes may be involved in both …

Design And Sythesis Of Conjugages Of Amphiphilic Cell-Penetrating Peptides Containing Anticancer Drug And Ligand For Extra Cellular Matrix Biomarker To Provide Efficient Tumor-Targeting, Shang Eun Park

Pharmaceutical Sciences (PhD) Dissertations

Peptide-drug conjugates (PDCs) have emerging applications in the safer delivery of chemotherapeutics to the site of diseases to avoid the side effects associated with the drug. PDCs also improve the physicochemical property of the anticancer drug. Therefore, we have designed and synthesized various conjugates of anticancer drugs with cancer- targeting peptides using established biomarkers of cancer such as the integrin receptor and extra-domain of fibronectin (EDB-FN) at the extracellular matrix. In the first studies, a series of targeting peptides targeting EDB-FN were synthesized and conjugated to different anticancer drugs. The synthesis, characterization, stability, and hydrolysis were performed. Cell viability studies …

Color And Structural Modifications Of Alkaline Extracted Sunflower Protein Concentrates And Isolates Using L-Cysteine And Glutathione, Akira Ishii

Food Science (MS) Theses

Sunflower protein can be extracted at alkaline pH with sulfites or organic solvent de-phenolization of sunflower seed meals if greening is unwanted. This greening is promoted at alkaline pH when chlorogenic acid (CGA) oxidizes and reacts with free amine groups from amino acids, such as lysine. Thiol-containing dough conditioners: L-cysteine hydrochloride and reduced glutathione (GSH) were investigated as an alternative de-greening strategy to de-phenolization. Varying pH from 7 to 11 and concentration of 0.82 to 5.6 mM were randomly assigned by Response Surface Methodology (RSM) to evaluate the combined and additive greening inhibition effect of thiol and extraction pH. The …

Structural Characterization And In Vitro Antiproliferative Activity Of Non-Specific Lipid Transfer Protein 1 (Nsltp1) From Fennel (Foeniculum Vulgare) Seeds, Mekdes Megeressa

Pharmaceutical Sciences (PhD) Dissertations

Non-specific lipid transfer proteins (nsLTPs) are cationic proteins involved in intracellular lipid shuttling, in growth and reproduction, as well as in defense against pathogenic microbes. Even though the primary and spatial structures of some nsLTPs from different plants indicate their similar features, they exhibit distinct lipid-binding specificities signifying their various biological roles that dictate further structural study. The present study determined the complete amino acid sequence, in silico 3D structure modeling, and in vitro antiproliferative activity of nsLTP1 from fennel (Foeniculum vulgare) seeds.

Fennel is a member of the family Umbelliferae (Apiaceae) native to southern Europe and the …

Amphiphilic Cell-Penetrating Peptides Containing Natural And Unnatural Amino Acids As Drug Delivery Tools And Antimicrobial Agents, David Salehi

Pharmaceutical Sciences (MS) Theses

Cell-penetrating peptides containing arginine as positively charged residues and tryptophan or diphenylalanine as hydrophobic residues were synthesized. The synthesis was accomplished through the Fmoc solid-phase peptide synthesis in the presence of HBTU and DIPEA. The side-chain protected linear peptides were cleaved from the resin and cyclized in the presence of DIC and HOAt in the solution phase overnight. MALDI-TOF mass spectrometry was used to characterize the peptides.

The cytotoxicity of the synthesized peptides was determined in CCRF-CEM (human, lymphoblast peripheral blood), and HEK-293 (human, embryonic epithelial kidney healthy) cells using the MTS assay. A concentration of 10 µM was found …

Viral Factors Influencing Early Infection Events During Ex-Vivo Kshv Infection, Ramina Nabiee

Pharmaceutical Sciences (PhD) Dissertations

The enigma of Kaposi Sarcoma Herpes Virus infection, and its persistence despite a quarter century of research on the virus, has given rise to an immediate need for addressing fundamental questions about basic immunology and virology knowledge regarding this virus. Kaposi Sarcoma Herpes Virus (KSHV), also known as Human Herpesvirus 8 (HHV8), is the etiological agent of Kaposi Sarcoma (KS) and other lymphoproliferative cancers, such as Multicentric Castleman’s Disease (MCD), Primary Effusion Lymphoma (PEL), and a newly discovered rare disease called KSHV Inflammatory Cytokines Syndrome (KICS). Epidemic KS, also known as AIDS-KS, is the most common cancer in untreated HIV …

Elucidating The Relation Between Human Milk Fatty Acids, Extracellular Vesicles, And Infant Developmental Outcomes In The First Year Of Life, Diana Bickmore

Food Science (MS) Theses

For most infants, human milk is the recommended source of nutrition. Improved developmental outcomes have been reported in infants that consume human milk compared to infant formula. Essential fatty acids (EFAs) confer health benefits. However, EFAs cannot be synthesized by the body, and therefore must be consumed in diet. Extracellular vesicles (EVs) are nanoparticles containing a lipid bilayer membrane and are present in human milk. Methods of EV isolation such as ultracentrifugation (UC) may not be feasible for the study of EVs in human milk due to the need for large sample volume, which may not be available. The objectives …

Impact Of Gamma Irradiation On Post-Harvest Disorders In 'Bartlett' Pears, Michelle Tu

Food Science (MS) Theses

The goal of this research was to determine the effect of irradiation on post-harvest disorders and ripening quality of ‘Bartlett’ pears stored for 3 months in air. ‘Bartlett’ pears were treated at 470 and 940 Gy and held at -1 - 0 ˚C at 95 % humidity. At 0, 45, and 90 days following treatment, the pears were brought to room temperature and allowed to ripen. The pears were then monitored for changes in respiration rate and ethylene production. After reaching the climacteric peak, pears were evaluated for incidence of post-harvest disorders, ACS and ACO enzyme activities, and quality factors …

Cluster Determinant 44 (Cd44) Receptor And Gout: Mechanistic Role In Pathogenesis And Therapeutic Targets, Emira Bousoik

Pharmaceutical Sciences (PhD) Dissertations

Gout is considered one of the most common forms of arthritis. It is characterized by sudden, severe attacks of pain, redness, and swelling in the joints. Management of acute gout attacks remains suboptimal, and hospitalizations due to poorly controlled flares have significantly increased over the past two decades. Colchicine is considered one of the first-line treatments for the relief of the symptoms associated with gout attacks. However, the use of colchicine for gout therapy has limitations due to the severe adverse effects, including fatalities. Acute gout is caused by deposition of monosodium urate (MSU) crystals in peripheral joints and surrounding …

Computational Molecular Docking Models And Design Of Diarylpentanoids For The Androgen Receptor, Jarett Guillow

Computational and Data Sciences (MS) Theses

The androgen receptor (AR) is a member of the nuclear receptor protein family that, upon binding to its natural ligand dihydrotestosterone (DHT) in the cytoplasm, translocates to the nucleus and exerts nuclear transcription factor activity to drive gene expression related to normal prostate development. AR signaling becomes overactive during the development and progression of prostate cancer through different mechanisms, including over-expression and mutation of the AR. Therefore, the AR is a prominent molecular target in the clinical management of prostate cancer. However, all therapeutic modalities targeting the AR, including androgen ablation therapy and AR block suffer from transient efficacy and …

Effect Of Dried Mushroom Powder On Thiol Content In Lyophilized And Native Bovine Myofibrillar Protein, Allany Chayasing

Food Science (MS) Theses

Thiol oxidation can form disulfide bonds that modify protein conformations, resulting in lower free thiol content. The effect of dried (lyophilized and oven-dried) mushroom powder (Agaricus bisporus or Pleurotus ostreatus) added to bovine lyophilized and native myofibrillar proteins (MP) on thiol oxidation was investigated. Mixtures of 10mg/mL MP with 0.1% and 0.2% mushroom powder in 0.3M NaCl were stored at 2ºC and 80 ºC for 10 days. Oven-dried A. bisporus had higher Folin-Ciocalteu reducing capacity at 8.05±0.71 gallic acid equivalent (GAE) mg/g compared to 4.97±0.20 GAE mg/g oven-dried P. ostreatus. Lyophilized P. ostreatus contained 164% more ergothioneine than …

Effect Of Low Dose Irradiation On Expression Of Genes Involved In Ethylene Biosynthesis Of 'Granny Smith' Apples, Brian Nyakundi

Food Science (MS) Theses

Superficial scald is a physiological disorder characterized by skin browning that appears during or after storage of ‘Granny Smith’ apples. The mechanism for scald development is not fully understood, but it is hypothesized that scald formation is related to increased ethylene production. In apples, low dose irradiation induced ethylene reduction appears to be directly related to prevention of superficial scald. However, the molecular basis of such an irradiation induced effect is not known. In this study, effort was made to better understand the molecular basis of the decrease in ethylene production in apple fruit after treatment with x-ray irradiation. ‘Granny …

Authentication Of Species In Bison Products Using Molecular Methods, Zerika Scales

Food Science (MS) Theses

American bison (Bison bison) meat is vulnerable to species substitution due to its high value and similar appearance to less expensive meats, such as beef from domestic cattle (Bos taurus). DNA barcoding of the cytochrome c oxidase subunit 1 (CO1) gene is a commonly used method to test for meat species mislabeling. However, due to historical hybridization between the American bison and domestic cattle, additional testing is required to confirm species. The objective of this study was to perform a market survey of products sold as bison meat and verify the species of each product using …

Labeling Compliance, Species Authentication And Net Weight Identification Of Frozen Fish Fillets Sold In Grocery Stores In Southern California, April Peterson

Food Science (MS) Theses

Proper labeling of seafood is important to prevent economic deception, promote consumer awareness, and prevent exposure of at-risk groups to certain allergens and toxins. The objective of this study was to investigate prepackaged frozen fish sold in Southern California for Country of Origin Labeling (COOL) compliance, species authentication, use of acceptable market names, net weights, and percent glaze. A total of 111 frozen fish fillets from 13 different fish categories were purchased from grocery stores in Southern California. The fish categories targeted for this study were: catfish, cod, flounder, halibut, mahi-mahi orange rough, pollock, salmon, swai, swordfish, tilapia, tuna, and …

Formation Of Maillard Reaction Products And Chlorogenic Acid-Quinone Induced Green Pigments In Gluten-Free Pretzels Made Using Sunflower Flour, Rashi Bhatnagar

Food Science (MS) Theses

The two color-developing reactions that occur when soft pretzels are baked using sunflower flour (SFF) in aqueous alkali environment are chlorogenic acid (CGA)-quinone induced greening and Maillard browning. This study aimed to determine how CGA content in two different SFFs containing 45% and 55% protein (Heliaflor^® 45 and 55, respectively) affected the formation of green trihydroxybenzacridine (TBA) and Maillard reaction products (MRPs) in soft baked pretzels. Pretzels were baked with five doughs prepared using a pre-blended gluten-free flour, consisting of sweet white rice flour, whole grain brown rice flour, potato starch, whole grain sweet white sorghum flour, tapioca flour, …