Biochemistry, Biophysics, and Structural Biology Commons^™

Characterisation Of Cholesterolcontaining Microparticles In Autoimmunity, Shuai Shuai Hu

Doctoral

In recent years, it has become apparent that sub-micron scale remnants of cells, called microparticles (MPs), are present in human circulation. MPs contain DNA, RNA, protein and lipids (such as cholesterol). Increased numbers of MPs are observed in autoimmune conditions such as Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA). This work aims to address the deficiency in the literature concerning MP cholesterol (MPC) by establishing reference values for MPC in a representative healthy population group, and by investigating the potential of MP cholesterol as a biomarker in autoimmunity.

Limited Sequence Diversity Within A Population Supports Prebiotic Rna Reproduction, Ryo Mizuuchi, Niles Lehman

Chemistry Faculty Publications and Presentations

The origins of life require the emergence of informational polymers capable of reproduction. In the RNA world on the primordial Earth, reproducible RNA molecules would have arisen from a mixture of compositionally biased, poorly available, short RNA sequences in prebiotic environments. However, it remains unclear what level of sequence diversity within a small subset of population is required to initiate RNA reproduction by prebiotic mechanisms. Here, using a simulation for template-directed recombination and ligation, we explore the effect of sequence diversity in a given population for the onset of RNA reproduction. We show that RNA reproduction is improbable in low …

Impact Of Seasonal And Host-Related Factors On The Intestinal Microbiome And Cestode Community Of Sorex Cinereus And Sorex Monticola, Katelyn D. Cranmer

College of Graduate Studies: Theses & Dissertations

The intestinal microbiome of mammals plays a significant role in host health and response to environmental stimuli and can include both beneficial native bacteria as well as parasitic worms. In this study, I examined the intestinal cestode and bacterial communities of two closely related species of shrew, Sorex monticola and Sorex cinereus, over a six month period in 2016. Specimens were collected approximately every three weeks from May to October from the Sangre de Cristo Mountains in Cowles, New Mexico. A total of 79 shrews were prepared with the gastrointestinal tracts removed and flash-frozen in liquid nitrogen. An additional …

Relationship Of Sociodemographic Factors With Serum Levels Of Vitamin D In A Healthy Population Of Pakistan, Khalida Iqbal, Najmul Islam, Naseema Mehboobali, Ali Asghar, Saleem Perwaiz Iqbal, Mohammad Perwaiz Iqbal

Department of Biological & Biomedical Sciences

High prevalence of vitamin D deficiency has been reported from Pakistan. Association of sociodemographic factors with vitamin D status has received little attention in this region. Therefore, we embarked on investigating the relationship of sociodemographic factors with vitamin D levels in a healthy Pakistani population. Venous blood from 226 healthy participants (age range 19-69 years) was collected and analyzed for serum concentrations of 25(OH) vitamin D [25(OH)D] and other related biomarkers. Demographic characteristics of the study participants were collected. Vitamin D deficiency (25(OH)D levels less than 20 ng/ml) was found to be 75% in this cohort. Gender, sunlight exposure and …

Some Current Trends And Challenges In Philippine Aquaculture, With An Emphasis On Synergies With Biodiversity Initiatives, Ronald Allan L. Cruz, Vikas Kumar, Janice A. Ragaza

Biology Faculty Publications

No abstract provided.

The Dna Dependent Protein Kinase Catalytic Subunit Maintains Genomic Stability, Brandon Lee Sklavanitis

Graduate Research Theses & Dissertations

GBM is the most common CNS derived malignancy diagnosed each year. The median survival time to date is between 14.6 to 16.7 months for patients suffering from the disease. Clinical trials and research has yet to yield a breakthrough treatment. The invasive nature of GBM to surrounding tissue typically poses a challenge for complete surgical resection of the tumor, and radiotherapy remains a predominant treatment modality. The NHEJ pathway is main repair pathway responsible for repairing lethal radiation damage. As a result, this study used the CRISPR-Cas9 system to genetically engineer two GBM cell lines lacking expression of an essential …

Comparative Tumorigenic Amino Acid Starvation And Integrated Stress Responses In Epithelial Vs. Mesenchymal Hcc Cells With Asct2 Or Lat1 Transporter Knockouts, Stephanie Lois Cooper Woodin

Graduate Research Theses & Dissertations

The previously established roles of the amino acid glutamine have recently been expanded to include not only protein and nucleotide synthesis, as well as contributing significantly to energy production via mitochondrial hydrolysis of glutamine to glutamate, but also the role of this molecule in the reductive carboxylation of α-ketoglutarate resulting in carbon atoms used in cell membrane biosynthesis. Additionally, glutamine participates in maintaining glutathione homeostasis as well as regulation of anabolic signaling. Given its central role in anabolic processes, glutamine is preferentially transported into human cancer cells at a significant rate as compared to normal cells. This distinction has prompted …

Disease Resistance In Wheat And Its Relatives, Ethan James Andersen

Electronic Theses and Dissertations

Plants have evolved a complex defense system against pests and pathogens utilizing many types of receptors, signaling factors, and defense compounds to detect pathogen presence and respond effectively. Since many pathogens have evolved immunesuppressing effectors used to reduce plant resistance, plants have evolved a family of receptors that detect pathogenic effectors as a result of an evolutionary arms race. These receptors contain Nucleotide-Binding Site and Leucine-Rich Repeat domains and are called NBS-LRR or NLR proteins. Many grasses possess huge genomes with hundreds of NLR-encoding genes, often found in clusters at the extra-pericentromeric regions of chromosomes, where unequal crossing over causes …

Aligning Best Practices In Student Success And Career Preparedness: An Exploratory Study To Establish Pathways To Stem Careers For Undergraduate Minority Students, Kimberly D. Kendricks, Anthony A. Arment, K. V. Nedunuri, Cadance A. Lowell

Journal of Research in Technical Careers

Undergraduate minority retention and graduation rates in STEM disciplines is a nationally recognized challenge for workforce growth and diversification. The Benjamin Banneker Scholars Program (BBSP) was a five-year undergraduate study developed to increase minority student retention and graduation rates at an HBCU. The program structure utilized a family model as a vehicle to orient students to the demands of college. Program activities integrated best K-12 practices and workforce skillsets to increase academic preparedness and career readiness. Findings revealed that a familial atmosphere improved academic performance, increased undergraduate research, and generated positive perceptions of faculty mentoring. Retention rates among BBSP participants …

From The Laboratory To The Vineyard—Evolution Of The Measurement Of Grape Composition Using Nir Spectroscopy Towards High-Throughput Analysis, Aoife Power, Vi Khanh Truong, James Chapman, Daniel Cozzolino

Articles

Compared to traditional laboratory methods, spectroscopic techniques (e.g., near infrared, hyperspectralimaging)provideanalystswithaninnovativeandimprovedunderstandingofcomplex issuesbydeterminingseveralchemicalcompoundsandmetabolitesatonce,allowingforthecollection of the sample “fingerprint”. These techniques have the potential to deliver high-throughput options for the analysis of the chemical composition of grapes in the laboratory, the vineyard and before or during harvest, to provide better insights of the chemistry, nutrition and physiology of grapes. Faster computers, the development of software and portable easy to use spectrophotometers and data analytical methods allow for the development of innovative applications of these techniques for the analyses of grape composition.

Mapping The Effects Of 5’ Untranslated Region Deletions On Translation Of 3a In Bmv Rna3, Courtney Marie Bozman

Graduate Research Theses & Dissertations

Brome mosaic virus (BMV) is a positive sense, single-stranded RNA virus that infects a wide array of plant hosts globally including: wheat, oats, maize, barley, and rye. Since its discovery in the 1940s, BMV has served as a model organism in uncovering the modalities of viral infectivity, composition, translation, and replication. In many viruses, it is typically imperative to recruit cellular machinery to produce viral proteins as their coding capacity is limited. Therefore, there are sequences and structures within the leader sequences allow them to be competitive with the eukaryotic mRNAs. Although BMV has been thoroughly researched in these other …

Regulator Of G Protein Signaling-12 (Rgs12) In Dopaminergic And Kappa Opioid Receptor-Dependent Signaling And Behavior, Joshua David Gross

Graduate Theses, Dissertations, and Problem Reports (ETD)

Dopaminergic neurotransmission is critically involved in the etiology and treatment of many psychiatric and neurological disorders. One modulator of dopaminergic neurotransmission is the kappa opioid receptor (KOR) -- a G protein-coupled receptor (GPCR) that is densely expressed within dopaminergic neurons and circuits. GPCRs are tightly regulated by a variety of intracellular signaling molecules, including Regulator of G Protein Signaling (RGS) proteins. Canonically, RGS proteins act as GTPase accelerating proteins (GAPs) on GTP-bound Ga subunits following GPCR activation, thereby hastening the rate at which GPCR-mediated G protein signaling is terminated. However, some RGS proteins exhibit more complex mechanisms of action on …

The Evaluation Of The Rapidhittm 200 On Degraded Biological Samples, Alice Kim

Graduate Theses, Dissertations, and Problem Reports (ETD)

DNA (deoxyribonucleic acid) has become an integral part of forensic science in the last couple of decades since its discovery to this application by Alec Jeffreys. Although there have been many advances throughout the years, the time it takes to obtain a DNA profile using conventional methods in a laboratory setting is approximately 24 to 72 hours. Due to this length of time and the increase in demand for DNA testing, it has caused a tremendous amount of backlog throughout the country. In 2009, the FBI (Federal Bureau of Investigation) in collaboration with the US Department of Defense of Homeland …

Immunomagnetic Beads Coupled With Anti-Ph-20 Antibodies To Isolate Sperm From Dna Mixtures For Sexual Assault Kit Application, Kayla Becks

Graduate Theses, Dissertations, and Problem Reports (ETD)

Sexual Assault Kits (SAKs) account for a large portion of DNA mixture samples that are processed within a forensic laboratory, most commonly in the form of vaginal swabs. A typical vaginal swab from a SAK contains the female victim's epithelial cells and varying concentrations of sperm cells left by the perpetrator. The key to analyzing these types of samples is to separate the mixture into male and female fractions. As such, there is a demand to develop novel techniques that have the capability of recovering as much of the male fraction as possible, specifically in cases where there is a …

Avoiding Adverse Effects: New Ideas In Drug Discovery For Targeting Pparγ, Trey M. Patton

Graduate Student Theses, Dissertations, & Professional Papers

Peroxisome proliferator-activated receptor gamma (PPARγ) has been a drug target to treat type 2 diabetes for the last 20 years when rosiglitazone and pioglitazone were approved by the FDA in 1999. While effective at increasing insulin sensitivity, these drugs cause serious adverse effects due to their full agonist characteristics. For that reason, drug discovery efforts have attempted to reduce or prevent the amount of agonist character of new PPARγ targeting ligands. Unfortunately, there have been no new FDA approved drugs for the receptor. There is a need for new ideas to produce better quality pharmaceuticals that lessen the impact of …

Tumor-Targeted Conjugated Polymer Nanoparticles With Encapsulated Iron And Its Biomedical Application For In Vitro Killing Of Melanoma Cell Lines Through Ferroptosis Assisted Chemodynamic Therapy (Cdt), Khalaf Jasim

Electronic Theses and Dissertations

Melanoma represents one of the most aggressive and lethal forms of skin cancer, with annually rising incidences throughout the world. Although chemotherapy modalities remain the mainstay of treatment, the therapeutic potential of chemotherapy typically is hampered by multidrug resistance (MDR) and nonspecific drug distribution that causes side-effects. To surmount such limitations, novel nanoformulations of low band-gap poly ({4,8-bis [(2-ethylhexyl) oxy] benzo [1,2-b:4,5-b?] dithiophene-2,6-diyl}{3-fluoro-2-[(2-ethylhexyl) carbonyl] thieno [3,4-b] thiophenediyl}) (PTB7) and poly [2,1,3-benzothiadiazole- 4,7- diyl [4,4-bis (2-ethylhexyl)- 4H-cyclopenta [2,1-b:3,4-b'] dithiophene-2,6-diyl]] (PCPDTBT) were fabricated by a reprecipitation method. These conjugated polymer nanoparticles were functionalized with the polypeptide endothelin-3 (EDN3-CPNPs) to target melanoma. The …

Studies Of Oxidative Damage, Brain Proteome, And Neurochemical Metabolites In Cognitive And Neurodegenerative Disorders: (1) Chemotherapy-Induced Cognitive Impairment; (2) Parkinson Disease Rat Model, Xiaojia Ren

Theses and Dissertations--Chemistry

The rate of cancer patients is increasing as the development of science and technology. Twenty million cancer survivors are estimated living in the United States by 2025. However, many cancer survivors show cognitive dysfunction, negatively affecting the quality of life. These cognitive impairments are recognized as chemotherapy-induced cognitive impairment (CICI), also called "chemo brain" by cancer survivors, including the diminished ability of memory and learning, hard to concentrate and focus, as well as diminution of executive function and processing speed. The etiologies and pathologies of CICI are complicated, especially in most cases the anti-cancer drug cannot cross the blood-brain barrier …

Investigation Of Amyloid Β Oligomer Dissociation Mechanisms By Single Molecule Fluorescence Techniques, Hope Cook Abdalla

Theses and Dissertations--Chemistry

Alzheimer’s disease (AD) is currently considered the most prevalent neurodegenerative disease and places a large financial burden on society as healthcare resources are limited and the disease does not have a cure. Alzheimer’s disease is characterized by the presence of amyloid beta (Aβ) plaques and neurofibrillary tangles; however current literature suggests Aβ oligomers are the main aggregating species leading to AD symptoms. Therefore, the underlying cause of Alzheimer’s, accumulation of amyloid beta, is currently being studied in hopes of developing treatment options. Our research aims at determining the mechanism and kinetics of Aβ oligomer dissociation into non-toxic monomers in the …

The Role Of Rmta In The Opportunistic Pathaogen Aspergillus Fumigatus, Roshan Dahal

Graduate Research Theses & Dissertations

The fungus Aspergillus fumigatus is an opportunistic human pathogen capable of causing

a life-threatening systemic lung infection known as invasive aspergillosis among immune compromised

patients. This group includes individuals infected with HIV, people with hematological

malignancies, solid organ transplant patients, persons with genetic immunodeficiency and cancer

patient undergoing chemotherapy. Due to the medical relevance of this organism, it is imperative

to discover novel genetic elements to design antifungal drugs against A. fumigatus dissemination,

virulence and survival during human infection. Previously, the putative arginine methyltransferase

gene rmtA was characterized in the model organism Aspergillus nidulans and the opportunistic

plant pathogen Aspergillus …

Hif-2 Regulation Of Amino Acid Transporter Expression In Hepatocellular Carcinoma Cells, Jason A. Misurelli

Graduate Research Theses & Dissertations

Hypoxia represents a major driver of the cancer phenotype in solid tumors, especially those of hepatic origin. Low oxygen availability triggers a complex cellular response which alters metabolism and promotes cellular invasion. Growing evidence suggests the amino acid glutamine, an important molecular currency for both energy producing reactions and biosynthetic pathways, plays an enhanced role in cancer cells under hypoxia. Hypoxia-inducible factors (HIFs) are transcription factors crucial for regulating the cellular response to low oxygen. Family member HIF-1 has been well studied, however, recent evidence suggests HIF-2 may have a regulatory role in amino acid transport and metabolism under hypoxia. …

Impact Of Conformational Change, Solvation Environment, And Post-Translational Modification On Desulfurization Enzyme 2'-Hydroxybiphenyl-2-Sulfinate Desulfinase (Dszb) Stability And Activity, Landon C. Mills

Theses and Dissertations--Chemical and Materials Engineering

Naturally occurring enzymatic pathways enable highly specific, rapid thiophenic sulfur cleavage occurring at ambient temperature and pressure, which may be harnessed for the desulfurization of petroleum-based fuel. One pathway found in bacteria is a four-step catabolic pathway (the 4S pathway) converting dibenzothiophene (DBT), a common crude oil contaminant, into 2-hydroxybiphenyl (HBP) without disrupting the carbon-carbon bonds. 2’-Hydroxybiphenyl-2-sulfinate desulfinase (DszB), the rate-limiting enzyme in the enzyme cascade, is capable of selectively cleaving carbon-sulfur bonds. Accordingly, understanding the molecular mechanisms of DszB activity may enable development of the cascade as industrial biotechnology. Based on crystallographic evidence, we hypothesized that DszB …

Illuminating Dna Packaging In Sperm Chromatin: How Polycation Lengths, Underprotamination And Disulfide Linkages Alters Dna Condensation And Stability, Daniel Kirchhoff

Theses and Dissertations--Chemistry

During spermiogenesis, somatic chromatin is remodeled and a vast majority (> 90%) of DNA histones are replaced by short arginine-rich peptides called protamines. This compaction is immense, with protamine-DNA self-assembly in sperm chromatin resulting in a final volume roughly 1/6th of a somatic nucleus. This near crystalline organization of the DNA in sperm is thought crucial both for the transport of the paternal genes as well as for the protection of genetic information as sperm chromatin is transcriptionally inactive and all DNA repair mechanisms are shut down.

Chapter 1 will include an overview of the topics discussed in this document, …

Detection Of Beta-Lactamase Variants In Municipal Wastewater And Fresh Water, Sunil Pandey

Masters Theses

The occurrence and spread of antibiotic-resistant genes (ARGs) are pressing public health problems worldwide. A key factor contributing to the spread of ARGs is lateral gene transfer. Wastewater treatment plants (WWTPs) are measured hot spots of microbial diversity and resistance because they receive polluted wastewater from diverse sources and contain a variety of different environments with dense bacterial loads. Due to the overuse of antibiotics the genetic capacities of microbes have profited. This helps every source of resistance gene and every means of horizontal gene transmission to develop the multiple mechanism of resistance to each antibiotic used clinically, agriculturally, or …

Functions Of Dfrp And Other Drg Pathway Genes In The Moss Physcomitrella Patens, Robert James Srygler

Graduate Research Theses & Dissertations

GTP binding proteins (G proteins) are molecular switches that regulate many aspects of physiology in all cells. DRG1 and DRG2 (Developmentally Regulated GTP-binding proteins) have been found in all eukaryotes examined. Amino acid identity across eukaryotes is about 65% within an orthologous group and 55% between paralogs of a single species. Although DRGs are likely involved in some aspect of translation regulation, details of their precise cellular functions are not known.

In addition to DRGs there are other genes/proteins that comprise the “DRG pathway.” DFRPs (DRG Family Regulatory Proteins) have been shown to physically and genetically interact with DRGs. Previous …

Multi-Scale Computational Studies Of Calcium (Ca2+) Signaling, Bin Sun

Theses and Dissertations--Chemistry

Ca²⁺ is an important messenger that affects almost all cellular processes. Ca²⁺ signaling involves events that happen at various time-scales such as Ca²⁺ diffusion, trans-membrane Ca²⁺ transport and Ca²⁺-mediated protein-protein interactions. In this work, we utilized multi-scale computational methods to quantitatively characterize Ca²⁺ diffusion efficiency, Ca²⁺ binding thermodynamics and molecular bases of Ca²⁺-dependent protein-protein interaction. Specifically, we studied 1) the electrokinetic transport of Ca²⁺ in confined sub-µm geometry with complicated surfacial properties. We characterized the effective diffusion constant of Ca²⁺ in a cell-like environment, which helps to understand …

Xylan Metabolism By Caulobacter Crescentus, Viet Bui

Masters Theses

Bacteria present unique opportunities to explore the molecular mechanisms of nutrient acquisition processes at single cell level under various experimental conditions. Caulobacter crescentus is a gram-negative oligotrophic environmental bacterium with adaptive physiological responses, such as slow growth or complete arrest of cell cycle, presence of sessile and motile progenies with the sessile cells growing stalk to enhance nutrient uptake for growth in low-nutrient conditions. Details of plant polysaccharide-derived carbon compound, such as cellobiose, maltose, and xylose utilization by C. crescentus can be found but molecular details or mechanisms of polysaccharide utilization, such as xylan, has not been reported. Database analyses …

Measuring The Impact Of Oesophagectomy On Physical Functioning And Physical Activity Participation: A Prospective Study, E.M. Guinan, A.E. Bennett, Suzanne Doyle, Luke O'Neill, J. Gannon, G. Foley, J.A. Elliott, J. O'Sullivan, J.V. Reynolds, J. Hussey

Articles

Background: Oesophagectomy remains the only curative intervention for oesophageal cancer, with defined nutritional and health-related quality of life (HR-QOL) consequences. It follows therefore that there is a significant risk of decline in physical wellbeing with oesophagectomy however this has been inadequately quantified. This study prospectively examines change in physical functioning and habitual physical activity participation, from presurgery through 6-months post-oesophagectomy. Methods: Patients scheduled for oesophagectomy with curative intent were recruited. Key domains of physical functioning including exercise tolerance (six-minute walk test (6MWT)) and muscle strength (hand-grip strength), and habitual physical activity participation, including sedentary behaviour (accelerometry) were measured presurgery (T0) …

Mllt3 Regulates Expression Of Genes Critical To Liver Metabolic Homeostasis, Jonathan Richard Dixit

Master's Theses

Hepatic steatosis (fatty liver) is increasingly prevalent in the US, and is characterized by triglyceride accumulation within hepatocytes. This is a direct result of an imbalance between lipid import, export, de novo lipogenesis, and beta oxidation. Hepatic steatosis can also progress to nonalcoholic steatohepatitis (NASH) which is characterized by increased hepatocyte damage, inflammation, and fibrosis. Further progression can lead to liver failure or hepatocellular carcinoma, requiring liver transplant or causing death. Our lab recently created Mllt3 conditional whole body knockout mice. These mice developed hepatic steatosis and NASH following Mllt3 deletion. MLLT3 is a master gene regulator that is part …

Analysis Of Aboral Spine Variation In The Forcipulate Sea Star, Pisaster Ochraceus (Brandt 1835), Angela Jordane Jones

Cal Poly Humboldt theses and projects

Rocky intertidal zones are highly dynamic environments that exhibit substantial spatial and temporal variation in abiotic conditions, which can drive body form variation and energy allocation within calcifying species. Wave exposure, specifically, has been shown to be a significant driver of skeletal and structural morphology in organisms including gastropods, bivalves, and sponges. Many of such organisms, from sponges to echinoderms, rely on calcium carbonate for structural support and protection.

In the phylum Echinodermata (named for possessing a ‘spiny skin’), research on the form and function of calcium carbonate spines is largely relegated to Class Echinodea (e.g., urchins and sand dollars) …

Structural Characterization Of Black Widow Spider Dragline Silk Proteins Crp1 And Crp4, Mikayla Shanafelt

University of the Pacific Theses and Dissertations

Spider dragline silk is a biomaterial with outstanding material properties, possessing high-tensile strength and toughness. In nature, dragline silk serves a central role during spider locomotion and web construction. Today, scientists are racing to elucidate the molecular machinery governing silk extrusion, attempting to translate this knowledge into a mimicry process in the laboratory to create synthetic fibers for a wide range of different applications. During extrusion, it has been established that biochemical and mechanical forces govern spidroin folding, aggregation, and assembly. In black widow spiders, at least 7 different proteins have been identified as constituents of dragline silk fibers. These …