Biochemistry, Biophysics, and Structural Biology Commons^™

The Delineation Of Platelet Pathology In Cardiometabolic Disease, Chi Peng

Theses and Dissertations--Pharmacology and Nutritional Sciences

Obesity is a multifactorial disease with many comorbidities leading to multiorgan dysfunction. Current studies point towards dysregulation of platelet signaling as a driver for increased risk of cardiovascular disease and stroke. The exact mechanisms remain elusive due to the complex interplay of factors involved, warranting the need to further understand how platelets are affected. Our preliminary data evaluating changes in platelet and coagulation parameters from bariatric patients showed that obesity did not affect platelet count or clotting time as demonstrated in INR values. However, female patients had increased bleeding events before surgery that were decreased after surgery. Due to limitations …

Practical Challenges In Delivering Dsrna For Woody Plant Protection, Zachary Bragg

Theses and Dissertations--Entomology

Unprecedented weather events associated with climate change, coupled with extensive anthropogenic stresses, have reduced the effectiveness of traditional forest pest management approaches, which can no longer keep pace with invasive species overwhelming naïve landscapes and native pests experiencing eruptive and expansive outbreaks. Double-stranded RNA-(dsRNA) mediated gene silencing, a type of RNA interference (RNAi), has been coopted for use as a biopesticide against a multitude of agricultural and horticultural pests and could serve as a powerful tool for woody plant protection. While effective initiation of gene silencing and subsequent mortality have been demonstrated in multiple tree pests, effective and efficient methods …

Role Of Autophagy-Related Genes In Lipid Transport For Efficient Replication Of Tombusviruses, Yuanrong Kang

Theses and Dissertations--Plant Pathology

Tombusviruses are positive-strand RNA viruses, which utilize numerous co-opted host factors and massive de-novo synthesized membrane resources to modify host membranes and form large viral replication organelles (VROs). Among plenty of host cellular processes, autophagy emerges as a potential membrane resource for VROs formation due to its ability to de-novo generate the double membrane structures, known as autophagosomes. Besides, as an important host defense pathway, autophagy is also a target for tombusviruses to prevent its antiviral activities. In this study, I identify the role of key autophagy related genes, Atg11, Atg8, and Atg2, which are involved in autophagosome formation, and …

Development Of Functional Plasmonic Nanoceria For The Ultrasensitive Detection Of Ebola Glycoprotein, Carissa A. Sutton

Graduate Theses/Dissertations

Infectious diseases have been increasing in both severity and prevalence, leading to increasing economic burdens and health concerns. Ebola hemorrhagic fever is an infectious disease that is both highly communicable and highly fatal. Current detection methods for the virus have high specificity and sensitivity but have long and/or complicated procedures that do not allow for early virus detection in highly affected areas. Compared to the lengthy procedure of reverse transcription-polymerase chain reaction (RT-PCR), real-time RT-PCR is more time-efficient; however, specificity and sensitivity are reduced. Since early detection of the virus is the only way to increase survival rates, sensitive detection …

Personalized Molecular Therapies For Advanced Non-Small Cell Lung Cancer: Overcoming Heterogeneity To Optimize Treatment Response And Clinical Outcomes, Zuan-Fu Lim

Graduate Theses, Dissertations, and Problem Reports (ETD)

Lung cancer remains one of the deadliest cancers. Novel, paradigm shifting treatments including immunotherapy and targeted therapies have recently been developed to cull the deadly effects of lung cancer, but many challenges remain. There remains a significant unmet need to accurately predict and optimally select for patients who will respond to immune checkpoint inhibitors (ICI) treatment. In Chapter 2 of this dissertation, we investigated a novel live single cell cytokine profiling lab-on-chip platform, IsoLight, using peripheral CD4+ and CD8+ T-cells for ICI biomarker development. A total of 55,175 single T-lymphocytes were analyzed in this proof-of-concept study. We found that an …

Exploring 3d Genome Interaction And Epigenetic Regulation Via Swi/Snf Complex And Deep Learning Models, Ruoyun Wang

Dartmouth College Ph.D Dissertations

The three-dimensional organization of the genome is fundamental in regulating gene expression and maintaining cellular function. This organization's complexities, influenced by epigenetic marks and chromatin remodeling complexes, are crucial for understanding genomic regulation. Among these, the SWI/SNF complexes are key, facilitating chromatin accessibility and regulating gene activity across cell types. The first part of my dissertation focuses on SWI/SNF complexes, exploring their role in chromatin remodeling and their impact on 3D genome architecture. Utilizing next-generation sequencing (NGS) techniques, this section investigates the interplay between these complexes and chromatin structure. During my research on the SWI/SNF complex, I was intrigued by …

Inflammation And Tumor Progression: The Differential Impact Of Saa In Breast Cancer Models, Daniel Wilhelm Olivier, Carla Eksteen, Manisha Du Plessis, Louis De Jager, Lize Engelbrecht, Nathaniel Wade Mcgregor, Preetha Shridas, Frederick C. De Beer, Willem J. S. De Villiers, Etheresia Pretorius, Anna-Mart Engelbrecht

Saha Cardiovascular Research Center Faculty Publications

Background: Previous research has shown that the Serum Amyloid A (SAA) protein family is intricately involved in inflammatory signaling and various disease pathologies. We have previously demonstrated that SAA is associated with increased colitis disease severity and the promotion of tumorigenesis. However, the specific role of SAA proteins in breast cancer pathology remains unclear. Therefore, we investigated the role of systemic SAA1 and SAA2 (SAA1/2) in a triple-negative breast cancer mouse model.

Methods: Syngeneic breast tumors were established in wild-type mice, and mice lacking the SAA1/2 (SAADKO). Subsequently, tumor volume was monitored, species survival determined, the inflammatory profiles of mice …

Development Of A Diaryl Oxazole-Based Cleavable Linker For Peptides, Evan Wolff

Honors Theses

The development of new cleavable linkers increases the diversity of compatible conditions for peptide discovery platforms. Potential applications for these linkers include high-throughput pharmaceutical candidate screening when utilized in Peptide Encoded Libraries (PELs). This thesis describes the development of a bifunctional diaryl oxazole-based cleavable linker that may be incorporated into compounds through Solid-Phase Peptide Synthesis (SPPS). This oxazole-based linker may be rapidly cleaved by cerium ammonium nitrate in aqueous conditions and is compatible with most natural amino acids and a variety of unnatural amino acids. This linker represents the first single-electron oxidant labile linker described to our knowledge and it …

Cyp6g2 Is The Major P450 Epoxidase Responsible For Juvenile Hormone Biosynthesis In Drosophila Melanogaster, Qiangqiang Jia, Liu Yang, Jiamin Wen, Suning Liu, Di Wen, Wei Luo, Weihua Wang, Subba R. Palli, Li Sheng

Entomology Faculty Publications

Background Juvenile hormones (JH) play crucial role in regulating development and reproduction in insects. The most common form of JH is JH III, derived from MF through epoxidation by CYP15 enzymes. However, in the higher dipterans, such as the fruitfly, Drosophila melanogaster, a bis-epoxide form of JHB3, accounted most of the JH detected. Moreover, these higher dipterans have lost the CYP15 gene from their genomes. As a result, the identity of the P450 epoxidase in the JH biosynthesis pathway in higher dipterans remains unknown.

Results In this study, we show that Cyp6g2 serves as the major JH epoxidase responsible for …

N(Alpha)-Acetyltransferase 40-Mediated Histone Acetylation Plays An Important Role In Ecdysone Regulation Of Metamorphosis In The Red Flour Beetle, Tribolium Castaneum, Sharath Chandra Gaddelapati, Smitha George, Anilkumar Moola, Karthi Sengodan, Subba Reddy Palli

Entomology Faculty Publications

Histone acetylation, a crucial epigenetic modification, is governed by histone acetyltransferases (HATs), that regulate many biological processes. Functions of HATs in insects are not well understood. We identified 27 HATs and determined their functions using RNA interference (RNAi) in the model insect, Tribolium castaneum. Among HATs studied, N-alpha-acetyltransferase 40 (NAA40) knockdown caused a severe phenotype of arrested larval development. The steroid hormone, ecdysone induced NAA40 expression through its receptor, EcR (ecdysone receptor). Interestingly, ecdysone-induced NAA40 regulates EcR expression. NAA40 acetylates histone H4 protein, associated with the promoters of ecdysone response genes: EcR, E74, E75, and HR3, and causes an increase …

The Mechanoreceptor Piezo Is Required For Spermatogenesis In Bombyx Mori, Zhongjie Zhang, Xiaojing Liu, Bo Hu, Kai Chen, Ye Yu, Chenxin Sun, Dalin Zhu, Hua Bai, Subba Reddy Palli, Anjiang Tan

Entomology Faculty Publications

Background The animal sperm shows high diversity in morphology, components, and motility. In the lepidopteran model insect, the silkworm Bombyx mori, two types of sperm, including nucleate fertile eupyrene sperm and anucleate unfertile apyrene sperm, are generated. Apyrene sperm assists fertilization by facilitating the migration of eupyrene spermatozoa from the bursa copulatrix to the spermatheca. During spermatogenesis, eupyrene sperm bundles extrude the cytoplasm by peristaltic squeezing, while the nuclei of the apyrene sperm bundles are discarded with the same process, forming matured sperm.

Results In this study, we describe that a mechanoreceptor BmPiezo, the sole Piezo ortholog in B. mori, …

Illuminating Function And Enabling Inhibition At The Protein-Membrane Interface Of Glutathione Peroxidase 4., Courtney L. Labrecque

Theses and Dissertations

Membrane proteins act as gateways to cells and are responsible not only for signaling, lipid transport, and cellular homeostasis, but they are also integral in disease pathologies. One class of membrane proteins, peripheral membrane proteins (PMPs), reside in aqueous compartments of the cell until they are recruited to the membrane to perform their function. Glutathione peroxidase 4 (GPx4) is a PMP enzyme responsible for engaging the membrane and reducing lipid hydroperoxides, thereby preventing cellular death via ferroptosis. Due to its central function surrounding ferroptosis, GPx4 is an interesting drug target that has recently gained interest for inflammatory diseases as well …

Environmental Implications Of Modern Food Production: An Analysis For The Conscious Consumer, Jessica T. Coming

Cal Poly Humboldt theses and projects

This project explores the pathways by which agriculture affects the environment and determines which foods have the greatest climate, water, and land impacts. Agricultural effects on the environment are extensive, from loss of habitat and declines in regional biodiversity to disruption of global nutrient cycles and climate change. Global food production accounts for 26-34% of annual anthropogenic greenhouse gas emissions, makes up 38-46% of habitable land, and is responsible for 70% of freshwater extraction. The effect of agriculture on the environment is most significantly dictated by what type of food is being produced. Animal-based food products consistently have the highest …

Functionalized Gold Nanoparticles And Halogen Bond Interactions With Neonicotinoid Pesticides, Molly Mccuen “Mackey” Sherard

Honors Theses

Neonicotinoid (NN) pesticides have emerged globally as one of the most widely used agricultural tools for protecting crops from pest damage and boosting food production. Unfortunately, some NN compounds, such as extensively employed imidacloprid-based pesticides, have also been identified as likely endangering critical pollinating insects like honey bees. To this end, NN pesticides pose a potential threat to world food supplies. As more countries restrict or prohibit the use of NN pesticides, tools are needed to effectively and quickly identify the presence of NN compounds like imidacloprid on site (e.g., in storage areas on farms or pesticide distribution warehouses). This …

Impact Of Hdac Inhibitors On The Efficiency Of Cardiomyocyte Differentiation, Lauren Mary Sargent

Honors Theses and Capstones

Heart disease and injury is the leading cause of death worldwide, with much of its severity caused by the low regenerative capacity of cardiomyocytes (CMs). One of the strategies to counteract the poor regeneration of CMs is the production of CMs via differentiating stem cells. However, the low efficiency of obtaining CMs from stem cells is an issue because there are numerous inconsistencies in the process. Histone deacetylase (HDAC) inhibitors have been researched as ways to increase efficiency of CM differentiation by increasing histone acetylation, and thereby allowing differentiation to occur more efficiently. In this study, the HDAC inhibitor, trichostatin …

Immune Signaling And Pathogenesis Of Enterocytozoon Hepatopenaei Infection In Pacific White Shrimp Litopenaeus Vannamei, Nutthapon Sangklai

Chulalongkorn University Theses and Dissertations (Chula ETD)

Enterocytozoon hepatopenaei (EHP) is an intracellular microsporidian parasite causing hepatopancreatic microsporidiosis (HPM), a disease that impairs the digestion and nutrients absorption of shrimp and leads to growth retardation and size variation. Our studies aim to comprehensively investigate the host’s immune responses to the EHP infection and the pathogenesis of the parasite. It was found that genes in Toll and JAK/STAT pathways, as well as antimicrobial peptides, were highly upregulated upon the EHP infection. Importantly, suppression of the JAK/STAT pathways resulted in a significant reduction of the c-type lysozyme (LvLyz-c) expression and the elevation of EHP copy numbers. These indicate a …

A Guide To Otoliths Of Minnesota Fishes, Baylor J. Short

Journal of Earth and Life Science

Investigations into the diet patterns of piscivores can provide crucial information on predator-prey relationships, population dynamics, and responses to changing ecosystems. However, digestive processes often remove or alter physical characteristics that are traditionally used to identify consumed fish. This problem has been addressed to some degree with advances in molecular technologies, although these methods can be costly and require specific training and equipment to do so. In contrast, bony structures such as otoliths, vertebrae, cleithra, and others frequently have morphologies that are unique among families, genera, and species. Because these structures are resistant to digestion, they can be used to …

Theoretical And Experimental Constraints For The Equation Of State Of Dense And Hot Matter, Rajesh Kumar, Veronica Dexheimer, Johannes Jahan, Jorge Noronha, Jacquelyn Noronha-Hostler, Claudia Ratti, Nico Yunes, Angel Rodrigo Nava Acuna, Mark Alford, Mahmudul Hasan Anik, Debarati Chatterjee, Katerina Chatziioannou, Hsin Yu Chen, Alexander Clevinger, Carlos Conde, Nikolas Cruz-Camacho, Travis Dore, Christian Drischler, Hannah Elfner, Reed Essick

All Faculty Open Access Publications

This review aims at providing an extensive discussion of modern constraints relevant for dense and hot strongly interacting matter. It includes theoretical first-principle results from lattice and perturbative QCD, as well as chiral effective field theory results. From the experimental side, it includes heavy-ion collision and low-energy nuclear physics results, as well as observations from neutron stars and their mergers. The validity of different constraints, concerning specific conditions and ranges of applicability, is also provided.

Cd46 Isoforms And Viral Receptor For Adenovirus Type 64d, Corina Stasiak

Honors Theses

Adenovirus Type 64 (Ad.64) belongs to the adenovirus subgroup D, which causes epidemic keratoconjunctivitis (EKC), otherwise known as viral pink eye. There is currently no known effective treatment for EKC. Membrane Cofactor Protein (CD46) is an integral membrane glycoprotein that, in previous studies, has been identified as a protein receptor for the closely related Ad.37. It has been determined that Ad.64 uses CD46 as a receptor on the cell surface in HeLa cells. CD46 is alternatively spliced when expressed to have different isoforms of interest, including the BC and C isoforms. Certain cell types, like A549 lung carcinoma cells, express …

Cd46 Is A Protein Receptor For Human Adenovirus Type 64, Alexander Michael Robertson

Honors Theses

Adenoviruses are important gene delivery vectors and causative agents for a variety of human diseases such as the common cold and gastrointestinal infections. Human adenovirus type 64 (Ad64; formerly 19c) and type 37 are associated with epidemic keratoconjunctivitis. Based upon its high homology and similar disease tropism to Ad37, we hypothesized that Ad64 would have the same protein receptor, CD46 (membrane cofactor protein), as Ad37. We show that a recombinant Ad64 containing an enhanced Green Fluorescent Protein transgene (Ad64.eGFP) enters Chinese hamster ovary cells expressing human CD46 (CHO-CD46) on the surface. Entry into human cervical carcinoma (HeLa) cells is increased …

Structural Phylogenetics Of A Family Dna Polymerases, Yagmur Bingul

Honors Theses

The transition from the RNA to the DNA world stands as an important event, demanding the emergence of enzymatic activities for DNA precursor synthesis, retro-transcription of RNA templates, and replication of single and double-stranded DNA molecules. The distribution of protein families associated with these activities across the three domains of life—Archaea, Eukarya, and Bacteria—adds layers of complexity to the narrative. While Archaea and Eukarya often share similar protein structures, structural biology shows homologous, but distinct, structures in Bacteria. On the other hand, viral polymerases emerge as a crucial part of genome replication and transcription. Their versatility, including RNA-dependent RNA polymerase, …

Heterocycles As Peptide-Based Cleavable Linkers, John Blobe

Honors Theses

As cancer cases continue to rise, the need for advancing the treatment options for cancer is ever increasing. Current cancer therapeutics, while effective at treating localized cancers and a fraction of advanced cancers, generally lack the specificity needed to target more advanced cancers. Recent advancements in cancer treatments have leveraged antibodies to target certain cancers. A class of drugs that utilize antibodies to deliver anti-cancer therapy preferentially to cancer cells, termed antibody-drug conjugates (ADCs), have been quite effective in treating certain advanced forms of certain cancers. These ADCs could be more effective if they could allow for the facile release …

Investigating A Potential Protein-Protein Interaction Between Transcription Factor Pax6 And Ribosomal Protein S20 (Rps20), Modupe Oladayo

All Master's Theses

The neocortex is the largest region of mammalian brains and is responsible for the complex cognitive abilities and behaviors of mammals. The neocortex of mature mammals is divided into concise areas, which process sensory information from ears, eyes, and touch receptors, and regulate conscious movement of muscles. The combined graded expressions of several transcription factors over the embryonic neocortical ventricular zone regulates the sizes of these functional areas in the adult neocortex. Although progress has been made in understanding how transcription factors affect neocortical patterning, additional research is required to fully understand the underlying molecular mechanism(s), which will contribute to …

Chemical Synthesis And Biological Application Of Sensitive Rna, Alexander T. Apostle

Dissertations, Master's Theses and Master's Reports

In the field of epigenetics - the dynamic collection of chemical modifications that overlay DNA/RNA - there is increasing interest in the potential for therapeutic and research-based utilization of the epitranscriptomics: those epigenetic modifications specific to RNA. Epitranscriptomics can give us a new approach to understanding and treating RNA viruses, like SARS-CoV-2. Given viruses are often found modified by human epitranscriptomic machinery, understanding how these modifications can modulate virulence is of high interest. We have shown that the N1-methyladensoine modification causes RNA synthesis termination in the SARS-CoV-2 replication complex, and thus may explain the differences in symptoms observed in individuals. …

Whole Genome Crispr-Cas9 Screens Identify Genes Contributing To Viral Entry And Phagocytosis, Md Saddam Hossain

Electronic Theses and Dissertations

CRISPR/Cas9 is a revolutionary technique for genome editing where Cas9 nucleases can be targeted to specific genomic sites by single-guide RNAs (sgRNAs) containing roughly 20-nucleotide sequences that are complementary to the target region. Double strand breaks created by Cas9 are repaired through non-homologous end-joining (NHEJ) in most cells, resulting in insertions and deletions leading to frame shift mutations in coding regions. Thus, the CRISPR-Cas9 system can be exploited for systematic evaluation of gene function relationships by whole genome screening. We also developed a CRISPR whole‐genome screen and counter‐screen strategy based on a pseudoviral platform that allowed identification of genes specific …

Using Virus Like Particle Conjugates Of Synthetic Targeting Compounds To Deliver Chemotherapeutic Drugs To Cancer Stem Cells, Austen W. Kerzee

Chemistry Theses

Cancer stem cells are a type of cell that have the properties of both cancer cells and stem cells. They can differentiate into other types of cancer cells, are resistant to conventional chemotherapeutics, and seem to contribute greatly to the metastasis and recurrence of cancer. Due to these properties, eliminating cancer stem cells would be greatly beneficial in the treatment of cancer. While there have been approved therapeutic methods for the removal of a few of the cancer stem cells types, treatment for most types of cancer stem cells are still in the experimental phase and have yet to be …

Compliance And Roughness In Relation To Gecko Locomotion, Brooklynn Campbell

Williams Honors College, Honors Research Projects

Geckos move efficiently through a variety of substrates, from swaying branches to wooden fences to the sides of structures. Previous studies have studied locomotion and adhesion on manmade and rough substrates; however, the work is limited when discussing locomotion and adhesion as a relationship of compliance and roughness. Ease of movement was quantified by speed, under the assumption that the faster a gecko moves, the easier it is for the gecko to cross the substrate. Gehyra oceanica geckos from Moorea, French Polynesia were tested on substrates varying in compliance and roughness with four different treatments in total. Compliance, roughness, and …

Atg11 And Atg9 Interaction In Selective Autophagy, Chimi Dolker Sherpa

Master's Theses and Doctoral Dissertations

Selective autophagy, induced by cellular stresses, degrades/recycles a specific cargo. Ithelps prevent diseases like Parkinson’s, Huntington's, cancer, and bacterial infections. It involves the formation of an autophagosome, a double-membrane vesicle that takes the cargo to the vacuole/lysosome for degradation. Atg11, the central organizer of selective autophagy, acts as a scaffold protein, interacting with Atg9, Atg1 and other Atg proteins. Our research focuses on finding mutations in Atg11 that specifically disrupt its interaction with Atg9 without affecting its dimerization or interaction with Atg1. We targeted residues 455-535 of Atg11 as a putative Atg9 interaction site, performing mutagenesis on four key residues …

A Phytochemical Analysis Of Secondary Metabolites In Eupatorium Serotinum, Elise Snow

Theses and Dissertations

Phytochemistry, a subset of Natural Products Chemistry, studies chemically derived products from natural substances. Advances in this field have important applications in medicinal research due to the distinctive and unique properties of natural compounds. All metabolites are produced from the metabolic cycle, which is a pathway that provides energy for the organism. These metabolic compounds vary greatly and are classified based on their function within the organism. Primary metabolites are abundant and contribute to organism growth, development, and maintenance of energy. Secondary metabolites are found in lesser quantity and correlate to natural defense mechanisms. For example, salicylic acid is a …

Benzene Exposure In Reproductive Biology: A Comprehensive Analysis Of Placental Response And Molecular Mechanisms In Trophoblast Function, Anthony Maxwell

Wayne State University Dissertations

The increase in environmental challenges and exposure to pollutants like benzene poses pressing concerns for reproductive health. This dissertation investigates the impact of benzene exposure during gestation on placental function, a key determinant for fetal development and pregnancy outcomes. Our work establishes that benzene exposure during pregnancy induces maternal immune activation, leading to increased rates of fetal resorptions, compromised fetal growth, and abnormal placental development. Intriguingly, we identify a sexual dimorphic response in male and female placentas to benzene exposure, attributable to inherent differences between male and female placental biology. On a molecular level, benzene is metabolized into hydroquinone in …