Biochemistry, Biophysics, and Structural Biology Commons^™

Durable Oxyfluoride Waste Forms For Salt Wastes From Molten Salt Reactors, Alevtina A. Maksimova, Jake W. Amoroso, Matthew Page, Gregory Morrison, Hans Conrad Zur Loye

Faculty Publications

Molten salt reactors (MSRs) are promising technology to replace traditional light and heavy water reactors in the near future. Waste management for MSRs, however, remains a pressing concern that needs to be resolved prior to realizing deployment of MSRs. Specifically, the generated salt waste needs to be safely sequestered, a task made difficult by the high solubility of the salt waste that can cause the release of radionuclides into the environment. This work demonstrates a new approach to immobilize multiple fluoride salts into a single waste form by converting highly-soluble fluorides to durable and stable oxyfluorides. Notably, we report a …

Racial Health Disparities Among Pregnant Women Of Color In New York City: Biological And Systemic Impacts, Kaylin Peña

Pitzer Senior Theses

Racial Health Disparities Among Pregnant Women of Color in New York City: Biological and Systemic Impacts

Abstract

This thesis aims to explore how racial health disparities, underrepresentation in gynecology, and socioeconomic barriers contribute to adverse pregnancy outcomes among women of color in New York City. Through an interdisciplinary approach that combines resources from medical anthropology and human biology, this research will examine the biological implications of chronic stress, specifically HPA axis dysregulation, and its role in maternal health outcomes. With the idea of intersectionality, as conceptualized by Kimberlé Crenshaw, the study analyzes the various effects of systemic inequities and social …

Using Rna Sequencing To Examine Encephalic Gene Expression In Cactus Mice, Sarah A. Nicholls

Honors Theses and Capstones

Many of the exact mechanisms by which desert-adapted animals avoid dehydration-induced complications are unknown, though there are likely ties to the general mammalian dehydration response, a multisystem process spearheaded by the brain. Peromyscus eremicus, the cactus mouse, can survive its whole life without intaking water and is commonly used as a model to study desert adaptations. In this study, we have used bulk transcriptomics to characterize the differential gene expression across hydrated and dehydrated P. eremicus in five major regions of the brain: the cerebral cortex (referred to throughout much of this paper as the cortex), hippocampus, thalamus, midbrain, …

Optimization Of Small-Scale Bioreactors For Increased Pdna Production And Yield, Laura M. Hills

Honors Theses and Capstones

No abstract provided.

The Relevance Of Dnajb1 Protein Dimerization Against The Human Neurodegenerative Diseases, Erina Kotreli, Trang Le, Szymon Ciesielski

Dean's Leadership Council Library Research Prize

All biological functions in living organisms depend on the activity of proteins, long molecules that must twist and fold into specific shapes to become functional. A subset of proteins known as molecular chaperones is essential for maintaining cellular health by assisting other proteins in folding correctly and refolding those damaged by stress. When proteins misfold and clump together, they can form toxic aggregates linked to many neurodegenerative diseases, including Alzheimer’s disease (AD), one of the leading causes of death in the United States. In AD, these protein aggregates form organized, elongated structures referred to as amyloid-like fibrils, which damage neurons …

Targeting Als: A Multi-Cellular Study On The Potential Therapeutic Role Of Azole-Based Compounds, Alisha R. Kennedy

Theses and Dissertations

Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, is a progressive neurodegenerative disorder that leads to the degeneration of motor neurons, which control voluntary muscle movements such as eating, speaking, and breathing. As these neurons are damaged, voluntary movement ceases, leading to a fatal outcome. The survival time of ALS patients varies, ranging from a few months to up to 10 years. Chapter 1 of this thesis provides an overview of ALS, highlighting the role of transactive response DNA-binding protein 43 (TDP-43), a key feature in ALS and other neurodegenerative diseases. The aggregation of TDP-43, particularly due to …

Development And Application Of Enhanced Sampling Techniques For Investigating Protein Interactions And Drug Discovery, Timothy Hasse

Wayne State University Dissertations

Understanding the dynamics of protein–protein and protein–ligand interactions is critical for elucidating biological function and guiding drug discovery. However, many such processes involve rare events and high energy barriers that are difficult to capture with conventional molecular dynamics (MD). Enhanced sampling techniques extend the reach of MD, enabling access to biologically relevant transitions and thermodynamic properties. In the first project, Gaussian accelerated MD (GaMD) was used to study the MEIG1–PACRG complex, a key regulator of sperm flagellar assembly. Simulations of wildtype and mutant MEIG1 (W50A, Y68A) revealed mutation-specific disruptions to the binding interface and identified druggable pockets, particularly on PACRG. …

Epigenetic Potential Remains Stable Over 100 Years After Introduction, Danielle Dawkins

College of Graduate Studies: Theses & Dissertations

Introduced species provide important insights into organismal behavioral responses. Epigenetic mechanisms are one of the various ways in which behaviors can be modified, particularly through DNA methylation. Through such mechanisms, phenotypic changes can occur in response to environmental changes, allowing an organism to be more plastic. Epigenetic potential (EP) represents the capacity for an organism to be epigenetically modified, and can be measured by counting CpG motifs; cytosine adjacent to guanine within a DNA sequence. Phenotypic plasticity as it relates to EP has been studied extensively in the house sparrow (Passer domesticus), a globally introduced songbird. It is …

Functional Characterization Of Vago In Black Tiger Shrimp Penaeus Monodon Ikk-Nf-Κb Signaling Pathway Against Viral Infection, Zittipong Nanakorn

Chulalongkorn University Theses and Dissertations (Chula ETD)

Cytokines serve as key regulators in innate antiviral defense. In crustaceans, research on cytokine-mediated immunity remains limited. A previous study in Penaeus monodon has demonstrated that PmVago proteins exhibit cytokine-like function by acting through the inhibitor of kappa B kinase-nuclear factor κB (IKK-NF-κB) cascade to defend against white spot syndrome virus (WSSV). In this study, five PmVago isoforms were identified, each showing differential transcriptional responses to pathogen challenges. Among them, PmVago1 and PmVago4 exhibited strong antiviral responses against WSSV infection. RNA interference of PmVago1 and PmVago4 increased shrimp susceptibility to WSSV infection with enhanced viral replication. Their suppression also disrupted …

Systematic Review Of Immunohistochemistry Protocols, Arpitha Parthasarathy

Pitzer Senior Theses

Immunohistochemistry (IHC) is an essential technique in biological research that allows for the visualization and localization of proteins within tissue samples. This systematic review analyzes the most effective, efficient and reproducible protocols for IHC. It focuses on three critical steps: freezing, cryosectioning, and staining of skeletal muscle tissues in mice models. A total of 41, 44, and 48 articles on freezing, cryosectioning, and staining techniques, respectively, were analyzed, from reputable sources in biology like PubMed and Web of Science. Results showed the following. For freezing, the use of isopentane combined with liquid nitrogen appeared to be the best method, minimizing …

Ubiquitin, Cavitand, And Nmr: 15n-1h Hsqc Analysis Of Cavitand Binding Domains On Ubiquitin, Grant Stucky

CMC Senior Theses

Ubiquitin and its derivatives through side chain modification are present in many of the degradation pathways for proteins found in neurodegenerative diseases. A non-toxic method for determining the amount of these proteins could have biosensing applications, but the binding domains of such proteins are not well characterized. ¹⁵N-¹H HSQC analysis of ubiquitin’s interactions with different concentrations of a small negatively charged host molecule called cavitand provides insight into the binding interactions with side chains on the protein such as lysine and arginine. This is done comparing the HSQC spectra of different concentrations of cavitand and ubiquitin to …

Creation Of A Dual-Fluorescence Reporter System To Assay Mirna Regulation Of Apobec3a, Tolulope D. Ajayi

All Graduate Theses, Dissertations, and Other Capstone Projects

MicroRNAs have an important role in regulating gene expression, including regulating the transcripts of the APOBEC3 family of cytidine deaminases. The APOBEC3 family is part of the immune defense against viral infection but has also been implicated in cancer progression. The hypothesis for this thesis is that specific miRNAs could be identified that regulate APOBEC3A (A3A) expression. I used molecular cloning and confocal microscopy to evaluate the miRNA-mediated silencing of A3A. A commercially available vector, psiCHECK-2, can be used to assay microRNA (miRNA) activity on specific targets. Molecular cloning was performed to modify the psiCHECK-2 Dual luciferase system (Renilla and …

Synthesis And Characterization Of Free Radical Scavenging Dendrimer Nanogels Via Cross-Linking Reaction-Enabled Flash Nanoprecipitation, Lin Qi, Da Huang, Huari Kou, Anna Chernatynskaya, Nuran Ercal, Hu Yang

Chemistry Faculty Research & Creative Works

This work reports the development and evaluation of dendrimer-based nanogels based on Poly amidoamine (PAMAM) dendrimer generation 5, engineered to act as a carrier with reactive oxygen species (ROS)-scavenging capabilities. We developed a cross-linking reaction-enabled flash nanoprecipitation method in which the cross-linking reaction occurs during the flash nanoprecipitation process to form a cross-linked nanostructure. Using this approach, an N-hydroxy succinimide (NHS)-functionalized ROS-responsive thioketal cross-linker (TK-NHS) was synthesized and utilized to cross-link DAB-core PAMAM dendrimer G5, resulting in the formation of G5-TK nanogels. The resulting nanogels were characterized using dynamic light scattering and transmission electron microscopy, and their cytocompatibility, irritancy, cellular …

Scalable Fabrication Of High-Payload Dendrimer-Based Nanoparticles For Targeted Atherosclerosis Therapy, Huari Kou, Lin Qi, Da Huang, Jiandong Wu, Honglan Shi, Hu Yang

Chemistry Faculty Research & Creative Works

Nanoparticle-based therapeutics hold promise for the treatment of atherosclerosis, but challenges such as low drug-loading capacity and a lack of scalable, controllable production hinder their clinical translation. Flash nanoprecipitation, a continuous synthesis method, offers a potential solution for scalable and reproducible nanoparticle production. In this study, we employed a custom-designed multi-inlet vortex mixer to perform cross-linking reaction-enabled flash nanoprecipitation, facilitating controlled and scalable synthesis of cross-linked Poly amidoamine (PAMAM) dendrimer nanoparticles. Notably, this approach allows simultaneous nanoparticle cross-linking and drug loading in a single step. The mannose moiety enabled specific targeting of macrophages via mannose receptors, enhancing the localization of …

Electrochemical Detection Of Prostate Cancer—Associated Mirna-141 Using A Low-Cost Disposable Biosensor, Alexander Hunt, Gymama Slaughter

Center for Bioelectronics Publications

Prostate cancer is the second leading cause of cancer-related deaths among men in the United States. The early detection of aggressive forms is critical. Current diagnostic methods, including PSA testing and biopsies, are invasive and often yield false results. MicroRNA-141 (miRNA-141) has emerged as a promising non-invasive biomarker due to its elevated levels in the urine of patients with metastatic prostate cancer. Here, a low-cost, paper-based electrochemical biosensor for the sensitive detection of miRNA-141 in synthetic urine is reported. The device employs inkjet-printed gold electrodes on photopaper, functionalized with thiolated single-stranded DNA-141 capture probes for specific target recognition. The biosensor …

Electrical Homeostasis Of The Inner Mitochondrial Membrane Potential, Peyman Fahimi, Lázaro A. M. Castanedo, P. Thomas Vernier, Cherif F. Matta

Bioelectrics Publications

The electric potential across the inner mitochondrial membrane must be maintained within certain bounds for the proper functioning of the cell. A feedback control mechanism for the homeostasis of this membrane potential is proposed whereby an increase in the electric field decreases the rate-limiting steps of the electron transport chain (ETC). An increase in trans-membrane electric field limits the rate of proton pumping to the inter-membrane gap by slowing the ETC reactions and by intrinsically induced electroporation that depolarizes the inner membrane. The proposed feedback mechanism is akin to a Le Chatelier's-type principle of trans-membrane potential feedback control.

Investigating The Role Of Fnci-1 In The Development And Function Of The C. Elegans Nervous System, Meagan Collins

Open Access Master's Theses

Fanconi Anemia (FA) is a rare human genetic disease caused by mutation of any of twenty-three genes on the FA pathway, which functions in the repair of DNA damage and the maintenance of genome stability. FA is clinically characterized by congenital abnormalities and a predisposition to aplastic anemia and malignancies. Recently, progressive neurological symptoms and abnormal neurological findings on imaging have been noted in FA patients, including cerebral and cerebellar lesions, calcification, necrosis, gliosis, and associated acute and chronic neurological symptoms; this constellation of symptoms has been termed Fanconi Anemia-Associated Neurological Syndrome (FANS).

To elucidate the molecular etiology of FANS, …

Estrogen Receptor-Mediated Effects Of Resveratrol On Muscle Function, David Ayi-Bonte

Open Access Master's Theses

Artemis missions are set to send the next man and the first woman back to the moon and enable long-term missions on the lunar surface. However, exposure to lunar gravity has significant physiological effects characterized by loss of muscle mass, weakness and decreased bone density. Nutraceutical countermeasures such as Resveratrol (RSV), a naturally occurring polyphenol, have been identified as promising strategies to preserve musculoskeletal health; however, its pleiotropic effect hinders our ability to identify the primary cellular pathways through which it delivers its benefits. Furthermore, its efficacy in simulated lunar gravity is unknown. Based on the benefits observed with RSV …

Investigating Regulation And The Regulome Of The Nucleic Acid Binding Protein Spovg Within Borrelia Burgdorferi, Timothy C. Saylor

Theses and Dissertations--Medical Sciences

Prior studies indicated Borrelia burgdorferi SpoVG protein was regulated, SpoVG binds specifically to a number of nucleic acids, and SpoVG binds to the non-variable section of the major virulence factor vlsE. Although a direct transcriptional activator or inhibitor was not elucidated, it is shown that SpoVG is regulated based on cell culture density independent of the growth rate of B. burgdorferi, indicating that SpoVG regulation is outside the scope of the alternative sigma factor RpoS. Using a dCas9 CRISPRi construct to target SpoVG resulted in protein expression trending towards upregulation of the BosR-RpoS regulon, and a marked decrease …

Discovery Of Photosynthetic Oxic N2-Fixation In Cyanobacteria Using Wet Lab And Machine Learning Approaches, James A. Young Iii

Electronic Theses and Dissertations

No abstract provided.

Characterization Of The Erv41-Erv46 Complex As A Retrograde Receptor For Misfolded Secretory Proteins, John Andrew Fuesler

Dartmouth College Ph.D Dissertations

The Endoplasmic Reticulum (ER), the site of secretory protein biosynthesis

provides a favorable environment to promote polypeptide folding, protein

oligomerization and export. Although the ER contains many chaperones and other

factors that assist in protein folding, this process is error prone. Eukaryotes have

evolved protein quality control checkpoints to maintain homeostasis in the secretory

pathway, however these processes are imperfect and may result in proteotoxicity

when toxic levels or aggregates of proteins arise. Mutations in proteins involved in

trafficking in the early secretory pathway are closely associated with disease states.

Therefore, it is of great interest to further understand how …

Molecular Interactions Between The Shellfish Pathogen Vibrio Coralliilyticus Re22 And The Probiont Phaeobacter Inhibens S4sm, Jessica Coppersmith

Open Access Dissertations

Oyster larvae aquaculture is an important industry, both economically and environmentally, helping to create sustainable food systems by supplying seed oysters to farms, and also to restoration projects aimed at building coastal resilience and improving water quality by rejuvenating wild populations. However, oyster larvae are highly susceptible to rapid mortality events, crashes, which can seriously impact the industry. One source of these crashes in hatchery systems is vibriosis, caused by pathogenic species of Vibrio bacteria that are ubiquitous in temperate coastal waters, and with rising surface water temperatures their prevalence and virulence are increasing. To prevent these larval crashes from …

Novel Methodology And Proof-Of-Concept For Proton Ct Using Spot Profile Rather Than Bragg Peak Location, Brett Albert Ruben

Open Access Dissertations

Proton radiation therapy offers a highly precise method for cancer treatment, theoretically providing superior dose deposition characteristics compared to conventional X-ray radiation therapy. Its steep and finite dose fall-off region allows for superior tumor coverage while reducing, though not eliminating, dose to surrounding healthy tissue. However, its full potential is limited by range uncertainties, particularly those arising from the reliance on X-ray-based imaging methods called computed tomography (CT) for proton-based treatment. CT image Hounsfield Units (HU) must be converted to stopping power ratios (SPR) as these ratios are the clinically relevant value for accurately planning particle interactions during proton therapy. …

Cloning, Expression, And Characterization Of Collagen Galactosyltransferases From Human, Sponge, And Sea Walnut, Jeong Seon Kim, Tingfei Chen, Botao Zhang, Tristin M. Miller, Marisa E. Gilliam, Houfu Guo

Molecular and Cellular Biochemistry Faculty Publications

Collagen is an extracellular matrix protein conserved across animals and viruses, with its function regulated by post-translational modifications of lysine residues. Specifically, certain lysine residues in collagen are hydroxylated to form hydroxylysine, which serves as an attachment site for hydroxylysine-linked glycosylation. This glycosylation process is initiated by collagen galactosyltransferases from the GT25 family, also known as GLT25D or COLGALT proteins. Despite their biological importance, efficient methods for expressing and isolating GLT25Ds have yet to be fully developed, and the biochemical mechanisms underlying their function still need to be better understood. To address this, we performed sequence alignment and phylogenetic analyses …

The Detection Of Multiple Human Papillomavirus (Hpv) Types Through The Development Of An Isothermal Dna Amplification Assay, Lauren Powell

Doctoral

Human Papillomaviruses (HPV) belong to the Papillomaviridae family, with over 200 known types classified into high-risk (HR-HPV) and low-risk (LR-HPV) groups based on their carcinogenic potential. While most HPV infections are asymptomatic and transient, persistent infection can lead to health issues, including cervical cancer. Given the high prevalence of HPV and its potential for malignant transformation, nucleic acid amplification assays have become a widely implemented tool for routine HPV testing. This study developed a real-time isothermal DNA amplification assay for the detection and differentiation of multiple HPV types. A universal primer set was designed to target a highly conserved region …

Investigating The Lyoprotective Properties Of An Antifreeze Protein From A Broadleaf Desert Shrub, Alexzandria Sheppard

Honors Theses and Capstones

Lyophilization, or freeze-drying, is an important preservation method for protein-based products, such as protein pharmaceuticals. However, the process introduces both freezing and drying stresses that can harm proteins. Here, we have studied the efficacy of AnAFP, a dehydrin-like antifreeze protein isolated from the broadleaf desert shrub Ammopiptanthus nanus, in reducing enzyme damage during freeze-drying, or lyophilization. We have shown that AnAFP can protect the model enzyme lactate dehydrogenase (LDH) from both freezing and dehydration damages during lyophilization with similar or better efficacy than 10% w/v sucrose and superior to that of another known antifreeze protein.

Site-Specific Modification Of Antibodies Utilizing Microbial Transglutaminase For Improved Immunoassay Performance, Emily Beitello

Theses and Dissertations

Immobilization strategies used for fixing antibodies to solid phase surfaces significantly contribute to the antigen capture capacity and influences the performance and sensitivity of immunoassays. Traditional methodologies result in the random orientation and/or the weak attachment of immobilized antibodies. Different formats of immunoassays scope in applicability to many fields of research and everyday use. Improving the efficiency of immobilizing antibodies in immunoassays is a beneficial endeavor to increase assay sensitivity. Here, we investigated the use of enzyme-mediated conjugation of antibodies to facilitate a highly oriented immobilization. Microbial transglutaminase (mTG) catalyzes the covalent bond formation between a plethora of primary amine …

Organic Geochemical Evidence For Life In Archean Rocks Identified By Pyrolysis-Gc-Ms And Supervised Machine Learning, Michael L. Wong, Anirudh Prabhu, Conel O'D. Alexander, H. James Cleaves Ii, George D. Cody, Grethe Hystad, Marko Bermanec, Wouter Bleeker, C. Kevin Boyce, Andrea Corpolongo, Andrew D. Czaja, Souvik Das, Robert R. Gaines, Daniel D. Gregory, John A. Jaszczak, Emmanuelle J. Javaux, Jaganmoy Jodder, Andrew H. Knoll, Martin Van Kranendonk, Katie M. Maloney, Nora Noffke, Robert Rainbird, Emersyn Slaughter, Eva E. Stüeken, Roger E. Summons, Frances Westall, Jasmina Wiemann, Shuhai Xiao, Robert M. Hazen

OES Faculty Publications

Throughout Earth’s history, organic molecules from both abiogenic and biogenic sources have been buried in sedimentary rocks. Most of these organic molecules have been significantly altered by geologic processes through deep time. Nonetheless, the nature and distribution of those ancient fragmentary organic remains have the potential to reveal diagnostic biomolecular information after billions of years of burial. Here, we analyzed 406 fossil, modern biological, meteoritic, and synthetic samples using pyrolysis gas chromatography and mass spectrometry. We explored these analytical data via supervised machine-learning methods to discriminate samples of biogenic vs. abiogenic origin, plant vs. animal phylogenetic affinity, and photosynthetic vs. …

Open Path Spectroscopic Detection Of The Hydroxyl Radical: A Comparison Between Broadband Cavity-Enhanced Absorption Spectroscopy (Bbceas) And Bbceas Coupled With A Fabry-Pérot Interferometer (Bbceas-Fp), Callum Flowerday, Ryan Thalman, Matthew C. Asplund, Samuel A. Badstubner, Adam K. Cook, Philip Lundrigan, Jaron C. Hansen

ScholarsArchive Data

Data collected by the BBCEAS and BBCEAS-FP instruments described in the paper "Open Path Spectroscopic Detection of the Hydroxyl Radical: A Comparison Between Broadband Cavity-Enhanced Absorption Spectroscopy (BBCEAS) and BBCEAS coupled with a Fabry-Pérot Interferometer (BBCEAS-FP)"

Microbial And Plant Biodiversity In Appalachian Agroecosystems And Their Implications For Soil Health, Kinsey Reed Close

Graduate Theses, Dissertations, and Problem Reports (ETD)

The sustainability of agricultural landscapes depends on understanding the complex interactions between plants, soil, and microbes. In Appalachia, a region shaped by complex terrain and long histories of human and ecological interaction, small family farms produce hay, livestock, and row crops. These agroecosystems, though often treated as “artificial” by many ecologists, have the potential to support both food production and biodiversity conservation if managed with an understanding of ecological complexity. This dissertation examines how plant and microbial diversity interact with soil and management to influence nutrient cycling, soil health, and long-term resilience in Appalachian agricultural systems. A literature review revealed …