Biochemistry, Biophysics, and Structural Biology Commons^™

Invited Perspective: Existing Rules For Disinfection By-Products Are Good, But They Are Not Enough, Susan D. Richardson

Faculty Publications

No abstract provided.

Amyloid Fibril Formation And Polymorphism : A Critical Role Of Sulfur-Containing Amino Acid Residues, Tatiana Quiñones-Ruiz

Legacy Theses & Dissertations (2009 - 2024)

Protein aggregation that results in the formation of amyloid fibrils has been linked to many neurodegenerative disorders, including Alzheimer’s disease and Parkinson’s disease. The sulfur atoms in methionine (Met) and cysteine (Cys) residues of proteins can be readily oxidized, significantly affecting their properties. Oxidation of sulfur-containing amino acids has recently been shown to affect protein fibrillation. This work presents novel findings on Cys and Met redox reactions that are related to the formation of amyloid fibrils and on the polymorphism of a model fibrillogenic protein, hen egg white lysozyme (HEWL). Biophysical techniques including Raman spectroscopy, atomic force microscopy, electron paramagnetic …

An Ims-Ms/Md Workflow For Determining Higher Order Structure And Dynamics Of Nucleic Acids, Rebecca D'Esposito

Legacy Theses & Dissertations (2009 - 2024)

Ion mobility spectrometry - mass spectrometry (IMS-MS) has potential for the investigation of structure and dynamics in large biopolymers, which will come to full fruition only with a firmer understanding of how to interpret the experimental data. Numerous studies have employed elements of nucleic acid (NA) secondary structure, such as duplexes and hairpins, to explore the relationships between structure, experimental conditions, and actual observations. When combined with molecular dynamics simulations (MDS), IMS-MS can be effectively employed to perform structural elucidation of biomolecules that are not readily amenable to established techniques employed for structural analysis.

N6-Methyladenosine Rna Modifications In Myogenesis / Narrative Competence And Cognitive Mapping As A Culturally Sustaining Pedagogy In The Education Of Emergent Bilinguals, Marina Danielle Infantado

Legacy Theses & Dissertations (2009 - 2024)

Myogenesis involves skeletal muscle stem cells (MuSCs) that produce and regenerate skeletal muscle during regular growth and repair. However, when this system fails to function normally, it can lead to musculoskeletal diseases like Duchenne Muscular Dystrophy (DMD). Therefore, it is important to study the molecular mechanisms behind this developmental process in order to seek therapies and solutions for these types of diseases. Our interest lies in the field of epitranscriptomics, which focuses on post-transcriptional ribonucleic acid (RNA) modifications, particularly N6-methyladenosine (m6A), which involves the addition of a methyl group to the adenosine nucleotide, a process that is mediated by the …

Parallel Networks That Govern The Transcriptional Response To Stress, Serene Anne Durham

Legacy Theses & Dissertations (2009 - 2024)

The transcription factor, p53, plays a pivotal role in the oversight of many stimulus-dependent pathways. Its ability to respond to a wide variety of cellular stress stimuli by activating a broad range of target genes has led it to be characterized as a stress-dependent transcription factor. Our research focuses on deconvoluting the varied transcriptional response to distinct stress signals in an attempt to define the regulatory strategies leading to gene activation after cell stress. We have found that distinct stress response networks, some of which are p53-independent, are converging at activation of a common set of target genes. Our data …

College Of Natural Sciences Newsletter, July & August 2022, College Of Natural Sciences

College of Natural Sciences Newsletters and Reports

Volume 3, Issue 5

Page 1 Dean's Message
Page 2 Awards & Recognition
Page 3 Resources for Student Success
Page 4 Welcome to New Faculty & Staff
Page 5 Summer Activities in CNS
Page 9 Celebrating the lives of those who touched the College
Page 10 Media Coverage of CNS
Page 12 Open PRAIRIE Data
Page 13 Snaps from he start of the semester
Page 14 Science as Art Competition

A Computational Model Of The Line-1 Retrotransposon Life Cycle And Visualization Of Metabolic Networks In 3-Dimensions., Michael D. Martin

Electronic Theses and Dissertations

Computational modeling of metabolic reactions and cellular systems is evolving as a tool for quantitative prediction of metabolic parameters and reaction pathway analysis. In this work, the basics of computational cell biology are presented as well as a summary of physical processes within the cell, and the algorithmic methods used to find time dependent solutions. Protein-protein and enzyme-substrate interactions are mathematically represented via mass action kinetics to construct sets of linear differential equations that describe reaction rates and formation of protein complexes. Using mass action methods, examples of reaction networks and their solutions are presented within the Virtual Cell simulation …

Investigating The Role Of The Three N-Terminal Hamp Domains Of The Aer2 Chemoreceptor From Pseudomonas Aeruginosa, Selina Anaya

Loma Linda University Electronic Theses, Dissertations & Projects

Pseudomonas aeruginosa is a ubiquitous environmental bacterium and opportunistic human pathogen. It readily adapts to changing environmental conditions with the aid of 26 chemoreceptors that signal to four distinct chemosensory systems. The Aer2 chemoreceptor from P. aeruginosa is an O2 sensor implicated in stress responses, virulence and fine-tuning the chemotaxis (Che) system. Aer2 is the sole chemoreceptor of the Che2 chemosensory system, which forms complexes at the cell pole during stationary phase. Aer2 is soluble, yet membrane-associated and displays an unusual arrangement with its PAS sensing domain sandwiched between three N-terminal and two C-terminal HAMP domains. HAMP domains are widespread …

An Analytical Method To Detect And Quantify Ll-37 In An In Vitro Co-Culture Of Activated Thp-1 Cells And Staphylococcus Aureus, Staphylococcus Epidermidis, And Pseudomonas Aeruginosa, Victoria Hunter

Graduate Theses and Dissertations

Healthcare-associated infections (HCAIs) affect 1.7 million hospitalized patients each year, resulting in over 98,000 deaths and anywhere from $28.4 to $45 billion in treatment costs. Furthermore, it has been established that more than 80% of these infections are caused by biofilms While HCAIs can be bacterial, viral, fungal, or parasitic, there are between 12 and 17 species cause 80 to 87% of all HCAIs. Among the most commonly isolated microorganisms are Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus). Thus, biofilms are of importance not only due to their prevalence in HCAIs but also due to the increased antibiotic …

Examining The Expression Patterns Of Desulfotalea Psychrophila Dsrab Operon And Pit At Subfreezing Temperatures And Different Concentrations Of Sulfate Salts As A Model For Mars And Icy Worlds Survival And Colonization, Sergio Luis Mosquera Mora

Graduate Theses and Dissertations

Since ancient times, Humanity has been fascinated with the idea of what lies beyond the borders of our planet. Fortunately, the combined efforts of many nations have made it possible to send unmanned spacecraft to orbit planets located close to Earth. These missions have the principal goal to collect data that could help us understand the basic environmental conditions that persist on those planets, or for evidence of past or present life. Equally important, landers and rovers have been successfully deployed to start the in-situ exploration of many planets of the Solar System. Among them, Mars has been extensively studied …

Validation Of Whole Genome Resequencing For Mapping The Genetics Of Ascites In Broilers And Viral Susceptibility In Layers, Katherine Pepper Lee

Graduate Theses and Dissertations

This dissertation focused on the efficacy and validity of whole genome resequencing (WGR) for fine mapping genetic determinants of particular traits in a given organism. Previously, our research group used WGR to identify haplotype blocks of single nucleotide polymorphisms associated with ascites resistance with some as strong candidates for use in marker-assisted selection (MAS). Chapter 2 discusses the completion of a MAS project through evaluation of ascites incidence as well as production traits of economic value to poultry producers. Thus, the MAS project also covered viability of this methodology in the industry. The MAS significantly reduced ascites incidence in broilers …

Characterization Of The Wee1 Homologues And The Investigation Of Factors Promoting Cellular Enlargement In Cryptococcus Neoformans, Rodney J. Colón Reyes

All Dissertations

Cryptococcus neoformans is an opportunistic fungal pathogen, infecting mainly immunocompromised individuals. As the main cause of cryptococcosis, it is responsible for over 180,000 deaths every year. As an environmental yeast, it has unique adaptations that allow it to proliferate in the human host. Among these adaptations its capacity to transition to an extreme phenotype known as Titan cells is of special interest to researchers. With sizes above 10 um and able to reach 70 um or more in cell size. This size is accompanied with a large vacuole, larger polysaccharide capsule, and an increased resistance to fluconazole (FLC). FLC is …

Development Of A Ph-Triggered Cargo Delivery System With Esxa Mutants, Shuchen Chen

Open Access Theses & Dissertations

Tuberculosis (TB) is a communicable disease caused by Mycobacterium tuberculosis (Mtb). It was the leading cause of human death generated by a single infectious agent before the Coronavirus (COVID-19) pandemic. Mtb has a special mechanism to evade the hostâ??s immune system and utilize macrophages as reservoirs. Latent TB infections have been a threat to public health. Liposome has been widely used for drug delivery. Immunoliposomes are special liposome carriers coated with ligands, such as antigens, targeting certain cells or organs to regulate the uptake of liposome. By constructing the liposome components, or surface modification, cargo release of liposome can be …

Eluication Of Lipid Metabolic Pathways In Differentiating Giardia Lamblia Using High Resolution Mass Spectrometry, Cameron Ellis

Open Access Theses & Dissertations

Giardia lamblia is an intestinal protozoan found worldwide, including the U.S. This parasite exists in two morphologic stages - a replicative trophozoite and a relatively dormant yet viable cyst. While exposures of cysts to gastric acid during passage through the human stomach induces excystation, factors in the small intestine, where trophozoites colonize trigger encystation or cyst formation. Transformation into cyst stage is essential for Giardia to survive in the environment for months before infecting new hosts. Because of its small genome size (11.7 Mb), metabolic pathways in Giardia are highly reduced. As far as lipid metabolism is concerned, only limited …

Characterization Of Esxa/Esxb Heterodimer Membrane Interaction With A Novel Popc/Popg Liposome Model, Salvador Vazquez Vazquez Reyes

Open Access Theses & Dissertations

EsxA and EsxB are co-secreted as a heterodimer and have been shown to play critical roles in phagosome rupture and translocation of Mycobacterium tuberculosis into the cytosol. Current in vitro studies support a model in which the EsxA:EsxB heterodimer is dissociated upon acidification, which might allow EsxA insertion into liposome membranes. While the membrane permeabilizing activity (MPA) of EsxA has been well characterized in liposomes composed of di-oleoyl-phosphatidylcholine (DOPC), the MPA of EsxA:EsxB heterodimer has not been detected with the DOPC liposome. In this study, we established a new in vitro membrane assay to test the MPA of EsxA and …

Role Of Pote Ankyrin Domain Family Member 2 (Pote-2) In Liver Cancer, Samantha Lopez

Theses and Dissertations

Liver cancer is the fifth leading cause of mortality attributed to cancer. Among various histological types, hepatocellular carcinoma (HCC) is the most prevalent form of liver cancer. There is a need to identify new biomarkers to help the physician, and allow them to decide what may be the most effective treatment for the patient. POTE-2 is one of the 14 paralogs apart of the ancestral POTE gene family. POTE-2 has been shown to be upregulated in non-small cell lung cancer and colorectal cancer, and is associated with increased migration, invasion, tumor size and poor survival. Evaluation of the Cancer Genome …

Characterization Of Genetic Pathways Involved In Resistance To A Novel Antifungal Peptide, Kayla L. Haberman

Graduate Theses and Dissertations

Antibiotic resistance is increasing prevalence, particularly in Candida glabrata. This opportunistic pathogen is closely phylogenetically related to Saccharomyces cerevisiae; however, its characterization is limited. C. glabrata is only second to Candida albicans as a fungal pathogen in immunocompromised patients. Commonly resistant to azoles, the most common fungal therapy, it has become costly and challenging to treat. A histatin 5 derived antifungal peptide, KM29, has a high degree of efficacy in Candida species and S. cerevisiae. The objective of this work is to advance our understanding of the mechanism of action of KM29 against C. glabrata. Previous work in the lab …

Improved Molecular Detection Tools For The Invasive Crop Pest Helicoverpa Armigera (Hübner), Mitchell D. Rich

All Theses

Helicoverpa armigera is a major crop pest native to Europe, Asia, Australia, and Africa. H. armigera has recently invaded South America and has caused billions of dollars in agricultural losses. It is difficult to differentiate H. armigera from H. zea, a closely-related species native to North and South America. A few genetic tests have been previously developed to detect H. armigera DNA in pooled samples of moth legs. In this study, an improved qPCR melt curve assay with higher detection sensitivity and a field-based recombinase polymerase amplification (RPA) assay were developed for specific detection of H. armigera DNA …

Metabolite Damage And Damage Control In A Minimal Genome, Drago Haas, Antje M. Thamm, Jiayi Sun, Lili Huang, Lijie Sun, Guillaume A.W. Beaudoin, Kim S. Wise, Claudia Lerma-Ortiz, Steven D. Bruner, Marian Breuer, Zaida Luthey-Schulten, Jiusheng Lin, Mark A. Wilson, Greg Brown, Alexander F. Yakunin, Inna Kurilyak, Jacob Folz, Oliver Fiehn, John I. Glass, Andrew D. Hanson, Christopher S. Henry, Valérie De Crécy-Lagard

Department of Biochemistry: Faculty Publications

Analysis of the genes retained in the minimized Mycoplasma JCVI-Syn3A genome established that systems that repair or preempt metabolite damage are essential to life. Several genes known to have such functions were identified and experimentally validated, including 5-formyltetrahydrofolate cycloligase, coenzyme A (CoA) disulfide reductase, and certain hydrolases. Furthermore, we discovered that an enigmatic YqeK hydrolase domain fused to NadD has a novel proofreading function in NAD synthesis and could double as a MutT-like sanitizing enzyme for the nucleotide pool. Finally, we combined metabolomics and cheminformatics approaches to extend the core metabolic map of JCVI-Syn3A to include promiscuous enzymatic reactions and …

Randomized Placebo-Controlled Trial Of Losartan For Pediatric Nafld, Miriam B Vos, Mark L Van Natta, Niviann M Blondet, Srinivasan Dasarathy, Mark Fishbein, Paula Hertel, Ajay K Jain, Saul J Karpen, Joel E Lavine, Saeed Mohammad, Laura A Miriel, Jean P Molleston, Marialena Mouzaki, Arun Sanyal, Emily P Sharkey, Jeffrey B Schwimmer, James Tonascia, Laura A Wilson, Stavra A Xanthakos, Nash Clinical Research Network

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: To date, no pharmacotherapy exists for pediatric NAFLD. Losartan, an angiotensin II receptor blocker, has been proposed as a treatment due to its antifibrotic effects.

APPROACH AND RESULTS: The Nonalcoholic Steatohepatitis Clinical Research Network conducted a multicenter, double-masked, placebo-controlled, randomized clinical trial in children with histologically confirmed NAFLD at 10 sites (September 2018 to April 2020). Inclusion criteria were age 8-17 years, histologic NAFLD activity score ≥ 3, and serum alanine aminotransferase (ALT) ≥ 50 U/l. Children received 100 mg of losartan or placebo orally once daily for 24 weeks. The primary outcome was change in ALT …

Sex-Specific Phenotypes In The Aging Mouse Heart And Consequences For Chronic Fibrosis, Aude Angelini, Jesus Ortiz-Urbina, Joann Trial, Anilkumar K Reddy, Anna Malovannaya, Antrix Jain, Mark L Entman, George E Taffet, Katarzyna A Cieslik

Faculty, Staff and Students Publications

The incidence of diastolic dysfunction increases with age in both humans and mice. This is characterized by increased passive stiffness and slower relaxation of the left ventricle. The stiffness arises at least partially from progressively increased interstitial collagen deposition because of highly secretory fibroblasts. In the past, we demonstrated that AMPK activation via the drug 5-aminoimidazole-4-carboxamide riboside (AICAR) in middle-aged mice reduced adverse remodeling after myocardial infarction. Therefore, as an attempt to normalize the fibroblast phenotype, we used 21-mo-old male and female mice and treated them with AICAR (0.166 mg/g body wt) where each mouse was followed in a functional …

Integrated Multi-Omic Characterization Of Congenital Heart Disease, Matthew C Hill, Zachary A Kadow, Hali Long, Yuka Morikawa, Thomas J Martin, Emma J Birks, Kenneth S Campbell, Jeanne Nerbonne, Kory Lavine, Lalita Wadhwa, Jun Wang, Diwakar Turaga, Iki Adachi, James F Martin

Faculty, Staff and Students Publications

The heart, the first organ to develop in the embryo, undergoes complex morphogenesis that when defective results in congenital heart disease (CHD). With current therapies, more than 90% of patients with CHD survive into adulthood, but many suffer premature death from heart failure and non-cardiac causes1. Here, to gain insight into this disease progression, we performed single-nucleus RNA sequencing on 157,273 nuclei from control hearts and hearts from patients with CHD, including those with hypoplastic left heart syndrome (HLHS) and tetralogy of Fallot, two common forms of cyanotic CHD lesions, as well as dilated and hypertrophic cardiomyopathies. We …

Applications Of Nuclear Magnetic Resonance Spectroscopy: From Drug Discovery To Protein Structure And Dynamics., Mark Vincent C. Dela Cerna

Electronic Theses and Dissertations

The versatility of nuclear magnetic resonance (NMR) spectroscopy is apparent when presented with diverse applications to which it can contribute. Here, NMR is used i) as a screening/ validation tool for a drug discovery program targeting the Phosphatase of Regenerating Liver 3 (PRL3), ii) to characterize the conformational heterogeneity of p53 regulator, Murine Double Minute X (MDMX), and iii) to characterize the solution dynamics of guanosine monophosphate kinase (GMPK). Mounting evidence suggesting roles for PRL3 in oncogenesis and metastasis has catapulted it into prominence as a cancer drug target. Yet, despite significant efforts, there are no PRL3 small molecule inhibitors …

Determination Of The Functional Role Of Rab-Ggt In Physcomitrium Patens., Hyun Jin Jung

Electronic Theses and Dissertations

Protein prenylation, a common lipid post-translational modification, is required for growth and development in eukaryotes. Rab geranylgeranylation involves the addition of one or two 20-carbon geranylgeranyl moieties to Rab-GTPase target proteins, which regulate intracellular vesicle trafficking. The reaction is carried out by heterodimeric Rab geranylgeranyltransferase (Rab-GGT), which is composed of two associated α- and β-subunits, with the assistance of an additional protein called Rab escort protein (REP). Loss of function of the Rab-GGT α subunit RGTA1 has not been reported in any plant. While knockout of either of the two β subunits RGTB1 or RGTB2 results in …

Improving The Ribozyme Toolbox: From Structure-Function Insights To Synthetic Biology Applications, Jessica Michelle Roberts

Boise State University Theses and Dissertations

Self-cleaving ribozymes are a naturally occurring class of catalytically active RNA molecules which cleave their own phosphate backbone. In nature, self-cleaving ribozymes are best known for their role in processing concatamers of viral genomes into monomers during viral replication in some RNA viruses, but to a lesser degree have also been implicated in mRNA regulation and processing in bacteria and eukaryotes. In addition to their biological relevance, these RNA enzymes have been harnessed as important biomolecular tools with a variety of applications in fields such as bioengineering. Self-cleaving ribozymes are relatively small and easy to generate in the lab using …

Regulation Of Systemic And Cellular Metabolism In Prostate Cancer By Camkk2 And Elucidation Of Atgl’S Role In Disease Progression, Dominik Awad

Dissertations and Theses (Open Access)

The androgen receptor (AR) is the major driver of prostate cancer; hence, men with progressing disease are treated with androgen deprivation therapy (ADT). However, the majority of patients will relapse within 2-3 years due to multiple AR reactivation mechanisms. Thus, AR and the processes downstream of the receptor remain central drivers of prostate cancer. A direct target of AR is CAMKK2, a gene coding for the serine/threonine kinase Ca^2+/calmodulin-dependent protein kinase kinase 2 (CAMKK2), a protein upregulated in advanced prostate cancer. CAMKK2 modulates many of its pathological effects through the phosphorylation and activation of the 5' AMP-activated …

Grk3 Connects Angiogenesis And Neuroendocrine Differentiation In Prostate Cancer By Activating Hdac2 That Epigenetically Represses Tsp1 And Rest, Samira Naderinezhad

Dissertations and Theses (Open Access)

Prostate cancer (PCa) is the second most frequent cancer and the second leading cause of mortality in men in the United States. Neuroendocrine prostate cancer (NEPC) is the aggressive subset of castration-resistant prostate cancer (CRPC), found in ~20% lethal CRPC. The mechanisms underlying the progression of PCa to NEPC are still largely unclear, and new drug targets are desperately needed. NEPC is highly vascularized (angiogenic) and characterized by high expression of neuroendocrine markers. However, direct molecular links connecting angiogenesis and neuroendocrine differentiation are elusive.

Since epigenetic regulation has been implicated in NEPC progression, we examined expression patterns of 147 epigenetic …

The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with dismal prognosis. The only curative option for patients is surgery, but over 80% of patients are not surgical candidates. Unfortunately, PDAC is resistant to the three remaining options. PDAC is characterized by a profoundly hypoxic and immunosuppressive stroma, which contributes to its therapeutic recalcitrance. Alpha-smooth muscle actin+ (αSMA+) cancer-associated fibroblasts (CAFs) are the most abundant stromal component, as well as mediators of stromal deposition. The hypoxia-inducible factors (HIF1 and HIF2) coordinate responses to hypoxia, yet, despite their known association to poor patient outcomes, their functions within the PDAC tumor microenvironment (TME) …

Lipid Composition And Configuration Drive Biophysical Properties Of The Mammalian Plasma Membrane, Jessica L. Symons

Dissertations and Theses (Open Access)

In the 1970s, it was established that phospholipid (PL) classes are asymmetrically distributed across the (PM) leaflets. Recapitulating strategies coupled with newly developed, high-resolution shotgun lipidomics, our lab confirmed PL class asymmetry and surprisingly measured the endoplasmic leaflet to contain double the number of PLs vs. the exoplasmic leaflet. My re-analysis of classical studies show that PM PL abundance imbalance has been a consistent finding across decades of literature. This is surprising, because bilayers do not tolerate interleaflet area imbalances to the degree that this imbalance would suggest, which prompted us to consider the existence of an elusive membrane resident …

Investigating The Biochemical Properties Of A Novel Mutation, A194v, In Human Rad51, Briana Vollbeer

All Theses

DNA double-strand breaks (DSB) are one of the most serious DNA lesions because improper repair of a DSB can lead to loss of heterozygosity, aneuploidy, and cancer. One of the primary pathways to repair DSBs is homologous recombination (HR). HR resects the DNA around the DSB and then uses homologous DNA as a template to restore the broken sequence. RAD51 has a vital function in this pathway by forming a nucleoprotein filament on a resected end of the DSB. The nucleoprotein filament searches for homology within the homologous DNA. Once homology is located, strand invasion followed by strand exchange occurs. …