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Articles 31 - 60 of 7023
Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
Comparative Screening Of Cytotoxic Potential Of Berberis Aristata And Senna Alexandrina Extracts, Rida Noor Akhtar, Javaria Zahoor, Rizwan Ullah Khan, Aziz Ullah, Naila Malkani
Comparative Screening Of Cytotoxic Potential Of Berberis Aristata And Senna Alexandrina Extracts, Rida Noor Akhtar, Javaria Zahoor, Rizwan Ullah Khan, Aziz Ullah, Naila Malkani
Journal of Bioresource Management
Medicinal plants provide a safe and efficient source of drugs for cancer treatment. Berberis aristata and Senna alexandrina are traditionally used to treat several ailments because they contain compounds with antimicrobial, antitoxic, anti-inflammatory, and other properties. The objective of the study was to prepare crude ethanolic extracts of B. aristata and S. alexandrina and to determine their cytotoxic potential against cancer cells. Ethanolic extracts were prepared for both plants. Hepatocellular carcinoma cells (HepG2) were used for all assays. The cytotoxicity of extracts was determined by 3‑(4,5‑Dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide (MTT) assay using various concentrations of extracts. The obtained sub-lethal concentrations were used …
Investigating Quinclorac Binding To Human Serum Albumin Using Spectroscopy And Molecular Docking, Le Nguyen, L. Hicks, L. Jodoin, S. Carby, D. S. Sanford, D. Benavides, A. Mishra, R. Yadav
Investigating Quinclorac Binding To Human Serum Albumin Using Spectroscopy And Molecular Docking, Le Nguyen, L. Hicks, L. Jodoin, S. Carby, D. S. Sanford, D. Benavides, A. Mishra, R. Yadav
Journal of the Arkansas Academy of Science
Human serum albumin (HSA) is the most abundant plasma protein and serves as a major transporter and reservoir for a wide range of endogenous ligands, including fatty acids, heme, bilirubin, prostaglandins, and metal ions, as well as numerous exogenous compounds, such as pharmaceuticals. HSA is a 66 kDa monomeric, multidomain protein containing two principal ligand-binding sites, Sudlow sites I and II. Sudlow site I contains Trp214, the sole tryptophan residue in HSA, whose intrinsic fluorescence provides a sensitive probe for studying ligand–protein interactions.
In this study, the interaction between HSA and the persistent organochlorine herbicide quinclorac (QNC) was investigated using …
In Silico And Toxicological Evaluation Of Crescentia Cujete Aqueous Extract: Potential Anticancer Activity Against Breast Cancer, Rahma Diyan Martha, Fatimah Fatimah, Syahputra Wibowo, Bantari Wisynu Kusuma Wardhani, Josephine Elizabeth Siregar, Elisabeth Farah Novita Coutrier, Alfia Fitrianita, Andri Pramesyanti Pramono, Ita Margaretha Nainggolan, Yudhi Nugraha, Danar Danar, Naufal Abiyyu, Lalu Unsunnidhal, Aswin Rafif Khairullah, Arif Nur Muhammad Ansori, Hesty Parbuntari, Wimbuh Tri Widodo
In Silico And Toxicological Evaluation Of Crescentia Cujete Aqueous Extract: Potential Anticancer Activity Against Breast Cancer, Rahma Diyan Martha, Fatimah Fatimah, Syahputra Wibowo, Bantari Wisynu Kusuma Wardhani, Josephine Elizabeth Siregar, Elisabeth Farah Novita Coutrier, Alfia Fitrianita, Andri Pramesyanti Pramono, Ita Margaretha Nainggolan, Yudhi Nugraha, Danar Danar, Naufal Abiyyu, Lalu Unsunnidhal, Aswin Rafif Khairullah, Arif Nur Muhammad Ansori, Hesty Parbuntari, Wimbuh Tri Widodo
Makara Journal of Science
Majapahit plant (Crescentia cujete), commonly found in Indonesia, has not been extensively explored for its medicinal properties. Given that many cancer treatments are derived from plants, this study aimed to examine the effects of plants on cancer chemical composition of the C. cujete fruit pulp extract, identify its primary compounds, and assess its potential as an antioxidant, anticancer agent, particularly for breast cancer. An insilico approach was used to evaluate the toxicity and interactions, of the compounds with cancer biomarker proteins, in addition to an in vivo Brine Shrimp Lethality Test (BSLT) for BSLT, toxicity screening using six …
Rna G-Quadruplexes Function As A Tunable Switch Of Fus Phase Separation, Jenny L. Carey, Miyuki Hayashi, Emily A. Welebob, Laura R. Ganser, Huan Wang, Kerry Buckhaults, Jacquelyn A. Depierro, Zheng Shi, James Shorter, Sua Myong, Aaron R. Haeusler, Lin Guo
Rna G-Quadruplexes Function As A Tunable Switch Of Fus Phase Separation, Jenny L. Carey, Miyuki Hayashi, Emily A. Welebob, Laura R. Ganser, Huan Wang, Kerry Buckhaults, Jacquelyn A. Depierro, Zheng Shi, James Shorter, Sua Myong, Aaron R. Haeusler, Lin Guo
Department of Biochemistry and Molecular Biology Faculty Papers
Fused in sarcoma (FUS) undergoes liquid-liquid phase separation (LLPS) to support essential cellular functions, but aberrant phase transitions promote toxic aggregation in neurodegenerative disease. Short RNA oligonucleotides can reverse this behavior, yet the structural determinants that govern RNA activity remain poorly defined. Here, we identify RNA G-quadruplexes (rG4s) as tunable structural motifs that potently modulate FUS LLPS. rG4 activity depends on its concentration and is modulated by rG4 length and stability: increasing repeat number switches rG4s from inhibitor to nucleator of FUS assembly, whereas chemical modifications that stabilize rG4 enhance inhibitory function and render these activities resilient to ionic perturbation. …
Histone Deacetylases In Kidney Injury: Distribution, Injury-Specific Regulation, And Fibroblast Hdac1 Function, Huy Nguyen
ETDs from 2020-2029
Acute kidney injury (AKI) is increasingly recognized as a major contributor to the development of chronic kidney disease (CKD) through maladaptive repair and interstitial fibrosis. Epigenetic regulation has emerged as a critical factor of kidney injury responses, however the injury-specific and cell-type specific roles of histone deacetylases (HDACs) remain poorly defined. This dissertation investigates the regulation and functional significance of HDACs in kidney injury, with a particular focus on fibroblast HDAC1 as a mediator of interstitial fibrosis development following AKI. In my cisplatin-induced AKI model, a single dose of cisplatin caused a significant decline in kidney function in both male …
Main-Chain Ion-Pair Polybenzimidazole Membranes Enabling Reduced-Temperature Ht-Pemfc Operation (Down To 120°C), Brian C. Benicewicz, Huina Lin
Main-Chain Ion-Pair Polybenzimidazole Membranes Enabling Reduced-Temperature Ht-Pemfc Operation (Down To 120°C), Brian C. Benicewicz, Huina Lin
Faculty Publications
Proton exchange membrane (PEM) fuel cells are promising for clean and efficient energy conversion across diverse applications. High-temperature PEM fuel cells (HT-PEMFCs) using phosphoric acid (PA)-doped polybenzimidazole (PBI) can operate up to 200°C, but at lower temperatures, water-induced PA loss often leads to performance degradation and reduced durability. In this work, we present a new class of main-chain ion-pair PBI membranes by integrating the imidazolium-biphosphate ion-pair units directly into the PBI backbone. This design results in membranes with high acid content, stronger acid-polymer interactions and stabilized acid retention. In single-cell tests, the Im+-PBI15-3 wt.% exhibits peak power densities of 0.79 …
Elucidating The Mechanisms Of Complex Flavoprotein Dehydrogenases, Tyler Alt
Elucidating The Mechanisms Of Complex Flavoprotein Dehydrogenases, Tyler Alt
Dissertations
Flavins are ubiquitous redox active cofactors that can catalyze electron transfer between substrates. They offer the advantage of being able to stabilize a range of oxidation and protonation states, as well being amenable to covalent modification, which can further alter their activity. As such, the scope of reactions catalyzed by flavoproteins is broad and flavin has implications in a range of biological processes. The two predominant forms of flavin that serve as redox active cofactors are flavin adenine mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which are functionally homologous. A major complication of studying flavoprotein dehydrogenases, and one that has …
Allosteric And Uncompetitive Inhibition Of Yeast Alcohol Dehydrogenase Identified By Enzyme Kinetics, Dylan Jeremy Harrison, Jenny A. Cappuccio
Allosteric And Uncompetitive Inhibition Of Yeast Alcohol Dehydrogenase Identified By Enzyme Kinetics, Dylan Jeremy Harrison, Jenny A. Cappuccio
IdeaFest: Interdisciplinary Journal of Creative Works and Research from Cal Poly Humboldt
Enzyme kinetics is a powerful technique used to quantify the rate at which an enzyme converts a substrate into a product and to identify potential inhibitors. In this study, kinetic analysis was employed to assess the activity of yeast alcohol dehydrogenase (YADH) in the presence and absence of sweeteners commonly found in alcoholic beverages. YADH catalyzes the oxidation of ethanol to acetaldehyde using NAD⁺ as a cofactor; the reduction to NADH can be monitored spectrophotometrically at 340 nm. Based on structural similarities to the ribose moiety of NAD⁺, it was hypothesized that sucrose and sucralose could directly interact with the …
Structure-Based Discovery Of Malate Dehydrogenase Inhibitors With Efficacy Against C. Parvum Oocysts, Ankita Bharatbhai Kheni
Structure-Based Discovery Of Malate Dehydrogenase Inhibitors With Efficacy Against C. Parvum Oocysts, Ankita Bharatbhai Kheni
Biochemistry and Molecular Biology
Cryptosporidium parvum, the etiological agent of Cryptosporidiosis (diarrheal illness) represents a significant global health burden, particularly affecting immunodeficient and pediatric populations. Since the parasite has a highly reduced mitochondrion and relies on glycolysis, enzymes such as C. parvum malate dehydrogenase (CpMDH), which are believed to be indispensable for parasite viability due to their pivotal roles in NAD⁺ regeneration and redox balance, remain largely unexplored as therapeutic targets. The present study employed a multifaceted experimental and computational strategy to evaluate the inhibitory activity of two lead-like and drug-like small molecules, referred to as compound 1.8 and compound 1.5, against the cofactor …
Terrestrial Abiotic Synthesis Of Simple Precursor Molecules Starting From Two Approaches: The Universality Of Carbon Reduction, Eloi Camprubi, Ben K.D. Pearce, Martina Preiner
Terrestrial Abiotic Synthesis Of Simple Precursor Molecules Starting From Two Approaches: The Universality Of Carbon Reduction, Eloi Camprubi, Ben K.D. Pearce, Martina Preiner
School of Integrative Biological & Chemical Sciences Faculty Publications
To address the chemistry responsible for life’s emergence, we examine the simple chemicals accessible on early Earth and the processes that could have transformed them. We focus on carbon reduction as a process central to the direct precursors of life. Two main approaches for the emergence of life’s building blocks and their associated functions are discussed. One approach investigates chemical routes for forming life’s building blocks via processes that worked differently from those of extant life, referred to as “unrestricted” prebiotic chemistries. The other approach establishes a direct mechanistic connection between prebiotic building blocks and extant biochemistry, referred to as …
Chromatin Insulators Homie And Nhomie Can Interact With Distant Copies Either Together Or Separately, With Distinct Outcomes For Enhancer-Promoter Interactions, Miki Fujioka, Wenfan Ke, Paul Schedl, James B. Jaynes
Chromatin Insulators Homie And Nhomie Can Interact With Distant Copies Either Together Or Separately, With Distinct Outcomes For Enhancer-Promoter Interactions, Miki Fujioka, Wenfan Ke, Paul Schedl, James B. Jaynes
Department of Biochemistry and Molecular Biology Faculty Papers
Chromatin insulators, a.k.a. boundary elements, separate regions of the chromosome with distinct chromatin characteristics, including distinct histone modifications. This activity affects gene expression by allowing chromatin domains to be stably regulated and maintained. Insulators also block enhancer-promoter interactions and, somewhat paradoxically, facilitate other interactions, particularly when they stitch together distant regions of the chromosome by pairing with specific partners. Here we explore how long-range interactions facilitated by insulator pairing are affected by the presence of two potentially competing partners. Our results show that when two partners are present, they can reduce each other's effects on distant gene expression, suggesting that …
Synthesis And Characterization Of Organometallic Polymers And Their Cytotoxicity Towards Human Cancer Cell Lines, Paul Peter Slawek
Synthesis And Characterization Of Organometallic Polymers And Their Cytotoxicity Towards Human Cancer Cell Lines, Paul Peter Slawek
Electronic Theses and Dissertations 2020 - Present
This research aimed to synthesize organometallic polymers from dialkyl (methyl, ethyl, butyl, cyclohexyl, and octyl) and diaryl (phenyl) tin dichlorides and three organic monomers, dipicolinic acid (DPA), chloramphenicol (CH), and isomannide (IS), using interfacial polymerization. Structure-activity relationships were investigated through physicochemical characterization (light-scattering photometry, proton NMR, and IR spectroscopy) and cytotoxicity was evaluated against six human cancer cell lines (AsPC-1, PANC-1, MCF-7, MDA-MB-231, HT-29, PC-3), with cisplatin serving as the reference standard.
Five DPA/tin polymers were synthesized, with IC50 values in the range of 0.60–0.71 μg/mL. Their cytotoxicity was significantly lower than that of cisplatin (0.0023-0.044 μg/mL), suggesting that …
Synthesis And Characterization Of Synergistic Bioactive– Organometallic Condensation Polymers, Francesca Isabel Mosca
Synthesis And Characterization Of Synergistic Bioactive– Organometallic Condensation Polymers, Francesca Isabel Mosca
Electronic Theses and Dissertations 2020 - Present
This research focuses on the synthesis and structural characterization of polymers with anticipated anticancer and antiviral properties by combining metal-containing Lewis acids, organotin dichlorides (R2SnCl2), Group 4 metallocene dichlorides (Cp2TiCl2, Cp2ZrCl2 and Cp2HfCl2), and triphenyl Group 15 metal dichlorides (Ph3AsCl2, Ph3SbCl2 and Ph3BiCl2), with biologically active Lewis bases, lamivudine, a synthetic nucleoside, and camphoric acid, a dicarboxylic acid, to achieve synergistic effect.
Five classes of polymers were synthesized using interfacial polymerization: lamivudine and organotin dichlorides, lamivudine and Group 4 metallocene dichlorides, camphoric acid and triphenyl Group 15 metal dichlorides, camphoric acid and organotin dichlorides, and camphoric acid and Group 4 …
Napier Grass (Pennisetum Purpureum) Meal Modulates Growth Efficiency, Gut Morphology, And Systemic Health In Broiler Chickens, Eric Lim Teik Chung, Yee Lyn Ong, Nazri Nayan, Muhamad Faris Ab Aziz, Faez Firdaus Abdullah Jesse, Faizal Andri, Arissara Sopawong
Napier Grass (Pennisetum Purpureum) Meal Modulates Growth Efficiency, Gut Morphology, And Systemic Health In Broiler Chickens, Eric Lim Teik Chung, Yee Lyn Ong, Nazri Nayan, Muhamad Faris Ab Aziz, Faez Firdaus Abdullah Jesse, Faizal Andri, Arissara Sopawong
The Thai Journal of Veterinary Medicine
Grass and leaf meals, which include vital phytocompounds, have the potential to be a natural and safe alternative to antibiotics in the poultry industry. Therefore, this study aims to assess Pennisetum purpureum leaf meal and its phytocompounds on the health performances of colored-broilers. A total of 216 unsexed Sasso chicks were assigned to six diet groups. The negative control (T1) received a commercial basal diet without antibiotics, while the positive control (T2) received the same diet with oxytetracycline (100 mg/kg). Groups T3 to T6 received no antibiotics and included P. purpureum meal at 1.25, 2.50, 3.75, or 5.00 grams per …
Hydroxamate Formation In The Lipopeptide Containing Siderophore Taiwachelin, Aaron J. Gringer, Kernen P. Agwaza, Isabel Da Fonseca, Pablo Sobrado
Hydroxamate Formation In The Lipopeptide Containing Siderophore Taiwachelin, Aaron J. Gringer, Kernen P. Agwaza, Isabel Da Fonseca, Pablo Sobrado
Chemistry Faculty Research & Creative Works
Cupriavidus taiwanensis is a nitrogen-fixing bacterium found in root nodules of the invasive tropical weed Mimosa pudica . C. taiwanensis has been shown to grow in environments contaminated with heavy metals such as Pb, Cu, and Cd. Taiwachelin, a recently identified siderophore produced by C. taiwanensis , is an iron chelator that contains a hydroxamate functional group for metal binding. In its biosynthesis, a flavin-dependent N-monooxygenase (NMO) was predicted to hydroxylate l -ornithine, leading to formation of the metal binding hydroxamate moiety. Here, we report the cloning, expression, and biochemical characterization of this enzyme, herein referred to as CtNMO. CtNMO …
Immunomodulatory And Signaling Molecules From Plant-Associated Bacteria: Toll-Like Receptor 4 Agonist Adjuvants And Diketopiperazine-Mediated Communication, Marian Romaine
Dissertations, Theses, and Capstone Projects
Medicinal plants and their associated microbiomes constitute a rich source of bioactive natural products with applications in immunotherapy and microbial ecology. Herbal formulations have long been valued for safe immune enhancement, while bacterial signaling molecules govern community behaviors critical to pathogenesis, symbiosis, and environmental processes. Bacterial lipopolysaccharides (LPS) from plant-associated Gram-negative bacteria have emerged as potent TLR4 agonists, yet their endotoxic potential limits direct use, and diketopiperazines (DKPs) serve as versatile quorum-sensing mediators capable of modulating biofilms in mixed microbial systems.
The work in this thesis comprises two independent but complementary research strands. The first strand pursued the engineering of …
Identifying Textual Predictors Of Early Termination In Clinical Trials In Medicine: An Explainable Machine-Learning Study, Rohan Ramnarain
Identifying Textual Predictors Of Early Termination In Clinical Trials In Medicine: An Explainable Machine-Learning Study, Rohan Ramnarain
Dissertations, Theses, and Capstone Projects
About one in five clinical trials in medicine ends early, wasting valuable resources and reducing the evidence available for developing life-saving medical treatments. This project uses a method called Trial2Vec, which is a self-supervised machine-learning method that converts clinical trial documents into dense numerical representations that capture their key design and clinical characteristics, to turn each proposed clinical trial’s written protocol into a compact numerical profile (a process referred to as embedding). These profiles are then paired with a predictive machine learning models to identify the words and phrases in the trial documents that can signal a higher risk of …
Structure Of Ergosteryl-Aspartate Synthase Reveals How An Entrapped Trna Is Used Like A Prosthetic Swinging Arm In The Synthesis Of Aminoacylated Sterols, Hanako Murayama, Nathaniel Yakobov, Nassira Mahmoudi, Sasha Legrosdidier, Nicolas Fournier, Solène Zuttion, Kanata Matsumoto, Michihiro Nishimura, Jingwei Ji, Bruno Senger, Laurence Huck, Howard Gamper, Yoshiaki Kise, Ralph Kleiner, Mathieu Frechin, Ya-Ming Hou, Hubert Becker, Yuzuru Itoh, Frédéric Fischer, Osamu Nureki
Structure Of Ergosteryl-Aspartate Synthase Reveals How An Entrapped Trna Is Used Like A Prosthetic Swinging Arm In The Synthesis Of Aminoacylated Sterols, Hanako Murayama, Nathaniel Yakobov, Nassira Mahmoudi, Sasha Legrosdidier, Nicolas Fournier, Solène Zuttion, Kanata Matsumoto, Michihiro Nishimura, Jingwei Ji, Bruno Senger, Laurence Huck, Howard Gamper, Yoshiaki Kise, Ralph Kleiner, Mathieu Frechin, Ya-Ming Hou, Hubert Becker, Yuzuru Itoh, Frédéric Fischer, Osamu Nureki
Department of Biochemistry and Molecular Biology Faculty Papers
Ergosteryl-3β-O-L-aspartate synthase (ErdS) catalyzes tRNA-dependent aspartylation of ergosterol, a lipid essential for fungal cell membrane integrity. However, the functional significance of ergosteryl-aspartate and the molecular mechanisms underlying its synthesis remain unclear. Here, we show that ErdS localization is highly dynamic and that Erg-Asp is required for proper hyphal growth, sporulation, and spore germination, and likely influences stress tolerance. The cryo-electron microscopy structure of ErdS revealed an unprecedented sterol-binding pocket. In addition, the structures in complex with a non-hydrolyzable Asp-N-tRNAAsp show a tRNA-guided intramolecular aminoacyl transfer mechanism between two functional domains of the enzyme. The CCA end of tRNAAsp undergoes a …
High-Throughput Robotic Ethanol Inhibition Assays For Engineered Thermophilic Biofuel Strains, Kevin He, Daniel Olson, Marybeth Maloney, Anthony Lanahan
High-Throughput Robotic Ethanol Inhibition Assays For Engineered Thermophilic Biofuel Strains, Kevin He, Daniel Olson, Marybeth Maloney, Anthony Lanahan
Wetterhahn Science Symposium Posters
Ethanol stress assays are commonly used to evaluate microbial tolerance, metabolic adaptation, and fermentation performance. However, manual liquid handling introduces variability across replicate wells and small-volume pipetting steps, limiting reproducibility and throughput. This study developed an automated OT-2 robotic workflow to generate replicated ethanol concentration gradients for high-throughput inhibition assays in engineered thermophilic biofuel strains. Kinetic plate-reader measurements were used to quantify ethanol-dependent growth responses under anaerobic fermentation conditions. The reasearch question is: How do engineered thermophilic biofuel strains differ in ethanol-dependent growth inhibition under anaerobic fermentation conditions, and can automated robotic assays improve the reproducibility of these measurements? Can …
Crystal Structure Of Mouse Dxo In Complex With The Udp-N-Acetylglucosamine Cap And Molecular Mechanism For The Decapping Reactions, Najeeb Ullah, Selom K. Doamekpor, Liang Tong
Crystal Structure Of Mouse Dxo In Complex With The Udp-N-Acetylglucosamine Cap And Molecular Mechanism For The Decapping Reactions, Najeeb Ullah, Selom K. Doamekpor, Liang Tong
Department of Biochemistry and Molecular Biology Faculty Papers
Noncanonical metabolite 5' caps have recently been identified on RNAs, and the DXO/Rai1 family of enzymes can remove these caps in eukaryotes. While the binding modes of NAD, FAD and dephospho-CoA (dpCoA) caps in the active site of mouse DXO have been determined, how DXO recognizes the UDP-glucose (UDP-Glc) and UDP-N-acetylglucosamine (UDP-GlcNAc) caps is not known. In addition, the molecular mechanism by which DXO catalyzes the decapping reactions is still poorly understood, especially the location of the water/hydroxide that attacks the scissile phosphate to initiate the decapping. Here we report the crystal structure of mouse DXO in complex with UDP-GlcNAc …
Combating Β-Lactamase Resistance: From Inhibitor Design To Substrate Evolution, Lian M.C. Jacobs
Combating Β-Lactamase Resistance: From Inhibitor Design To Substrate Evolution, Lian M.C. Jacobs
USF Tampa Graduate Theses and Dissertations
β-lactamase production by bacteria is a major mechanism of antibiotic resistance. These enzymes hydrolyze β-lactam antibiotics, preventing them from binding to and inhibiting PBPs. Although new β-lactam scaffolds and inhibitors are continually introduced into the clinic, resistance often emerges within a few years. Therefore, the development of cross-class inhibitors with novel scaffolds is critical to mitigate this resistance. In parallel, a deeper understanding of the structural and mechanistic basis of β-lactamase resistance is essential. Together, these approaches provide an effective strategy for combating antibiotic resistance.
The first project addressed the need of effective cross-class β-lactamase inhibitors capable of targeting SBL …
In Vitro Reversal Of Abc Transporter Mediated Multidrug Resistance In Human Ovarian And Non-Small Cell Lung Cancer Models, Alison K. Kellom, Pia D. Vogel
In Vitro Reversal Of Abc Transporter Mediated Multidrug Resistance In Human Ovarian And Non-Small Cell Lung Cancer Models, Alison K. Kellom, Pia D. Vogel
Biological Sciences Theses and Dissertations
One of the major causes of treatment failure in aggressive cancers is multidrug resistance (MDR), which is linked to the overexpression of membrane efflux proteins that export chemotherapeutics from cancer cells. This mechanism prevents chemotherapeutic drugs from reaching cytotoxic concentrations intracellularly, allowing the cancer to survive. Two primary mediators of this mechanism are P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP). P-gp and BCRP are transmembrane ATP-binding cassette (ABC) transporters that are frequently overexpressed in MDR cancers. They utilize the binding and hydrolysis of ATP to transport a diverse range of amphipathic molecules of varying size (Schinkel and Jonker, 2003), …
Microtubules In Breast Cancer: Exploring The Α/Β-Tubulin Toggle Switch And Its Implications In Human Breast Cancer, Annemarie Ianos
Microtubules In Breast Cancer: Exploring The Α/Β-Tubulin Toggle Switch And Its Implications In Human Breast Cancer, Annemarie Ianos
Student Theses and Dissertations
Microtubules, composed of a/b-tubulin heterodimers, play a central role in breast cancer tumor growth by polymerizing, leading to metastasis and depolymerizing, contributing to proliferation. Human enzymes protein kinase Ca (PKC-a) and cyclin-dependent kinase 1 (Cdk-1) mediate phosphorylation at sites a:Ser165 and b:Ser172, respectively, influencing the growth of microtubules. It is possible that alternating phosphorylation at these sites contribute to an a/b-tubulin “toggle switch” that mediates microtubule instability and tumor growth.
The project investigates the influence of the toggle switch model on microtubule stability by determining the impact of mutants (a:S165D, a:S165N, a:S165SP, b:S172SP and a:S165SP/b:S172S …
Computational Design Of Peptides And Proteins Through Machine Learning Approaches, Emily J. Hendrix
Computational Design Of Peptides And Proteins Through Machine Learning Approaches, Emily J. Hendrix
Chemistry and Chemical Biology ETDs
Advancements in machine learning have emerged as a pivotal tool in computational biochemistry, offering new advancements to address challenges in protein structure and function. However, current machine-learning approaches offer limited insight in understanding protein dynamics. The purpose of this work is to combine traditional physics-based computational tools, such as molecular dynamics and coarse-grained simulations, with recently developed AI-driven computational tools to bridge gaps and advance the understanding of proteins in both structural and dynamic aspects. I investigated several approaches such as (i) traditional physics-based methods to study protein conformation and ensembles; (ii) identifying a peptide inhibitor for the PICK1 PDZ …
Virus-Like Particle Peptoid Conjugate As A Triple-Negative Breast Cancer Targeting Delivery System, Ricky Zhu
Virus-Like Particle Peptoid Conjugate As A Triple-Negative Breast Cancer Targeting Delivery System, Ricky Zhu
Chemistry Theses
Triple-negative breast cancer (TNBC), an aggressive form of breast cancer, characterized by its lack of estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptors (HER2) poses a therapeutic challenge as common treatment options are rendered ineffective. Here is a strategy to develop a drug delivery system utilizing poly-glycinated LC129 8, a TNBC targeting peptoid, covalently attached to HK97 virus-like particles (VLP) containing a C-terminal LPETG sequence via a sortase mediated reaction. Using the properties of the cage-like structure of VLPs and the TNBC specificity of the LC129-8, high doses of chemotherapy can be efficiently loaded into the …
Skin Of Frog And Scale Of Dragon: Nutritional Cues, Life Cycle Kinetics, And Secretome Dynamics In Batrachochytrium Dendrobatidis, Naomi C. Okada
Skin Of Frog And Scale Of Dragon: Nutritional Cues, Life Cycle Kinetics, And Secretome Dynamics In Batrachochytrium Dendrobatidis, Naomi C. Okada
UNLV Theses, Dissertations, Professional Papers, and Capstones
Nearly 50% of amphibian species are at risk of extinction, making them the most threatened group of vertebrates on the planet. A major driver of these declines is the pathogenic chytrid fungus Batrachochytrium dendrobatidis (Bd), which causes the fatal skin disease chytridiomycosis. Since its discovery in the late 1990s, Bd has been directly implicated in the extinction of 90 species of amphibians and the declines of hundreds more. Despite this devastating ecological impact, relatively little is known about its basic cellular biology.
Bd has a multi-stage asexual life cycle consisting of a motile and infectious zoospore, which encysts (into a …
Bax Activation Through The N-Terminal Bh3-Like Domains Of Vdac1 And Vdac2, Autumn A. Peters
Bax Activation Through The N-Terminal Bh3-Like Domains Of Vdac1 And Vdac2, Autumn A. Peters
Honors Theses
Voltage-dependent anion channels (VDACs) are central to mitochondrial function by mediating metabolite diffusion across the mitochondrial outer membrane (MOM). Two isoforms, VDACs 1 and 2, are also implicated in apoptosis based on interactions with Bcl-2 family proteins that control this process, including Bax and Bcl-xL. Activation of the pro-apoptotic protein Bax by interaction with ‘BH3-only’ proteins, such as Bim or Bid, induces MOM permeabilization to signal apoptosis, yet accumulating evidence indicates VDACs 1 and 2 may also affect Bax. We discovered that the VDAC N-terminal domains contain high sequence similarity to the conserved BH3 domains within Bcl-2 family members that …
Functionalized Nanodiamonds As Binding Platforms For Single-Stranded Dna, Mallory A. Chapman
Functionalized Nanodiamonds As Binding Platforms For Single-Stranded Dna, Mallory A. Chapman
Honors Theses
Nanodiamonds (NDs) offer a promising platform for biomolecular applications due to their stability, biocompatibility, and three-dimensional structure. This study focused on developing a nanodiamond–DNA complex in which streptavidin-functionalized NDs would form a protective shell around biotinylated single-stranded DNA (ssDNA), creating a core–shell system like an “M&M” candy with DNA at the center and a protective coating on the outside. DNA has many uses in nanotechnology, including DNA origami, nanomachines, and drug delivery systems, but its degradation limits its practical use, making protective strategies essential.
ND–DNA conjugates were prepared using biotin–streptavidin interactions and analyzed using gel electrophoresis. Initial separation on agarose …
Unc-45b As A Potential Chaperone For The Transcription Factor, Gata-4, Kaylah Owings
Unc-45b As A Potential Chaperone For The Transcription Factor, Gata-4, Kaylah Owings
Electronic Theses and Dissertations
The cardiac myosin–specific chaperone UNC-45B has been shown to physically interact with the cardiac myosin transcription factor GATA-4. Specifically, this interaction occurs within the chaperoning region of UNC-45B, known as the UCS domain. However, the precise nature of this interaction has not yet been fully elucidated. The present study was conducted to confirm earlier findings and to evaluate whether UNC-45B functions as a chaperone for GATA-4 using bioinformatic approaches. Analysis of the interaction using AlphaFold 3 modeling verified not only that binding occurs at the UCS (chaperoning) domain of UNC-45B, but also that the interaction is associated with an increase …
Biochemical Characterization Of Luciferase In Omphalotus Olearius, James H. Martin
Biochemical Characterization Of Luciferase In Omphalotus Olearius, James H. Martin
Honors Theses
The overall goal of this thesis was to investigate the genetic basis of bioluminescence in Omphalotus olearius, a bioluminescent mushroom. The project initially focused on growing fungal cultures under controlled laboratory conditions and using molecular techniques such as DNA extraction, PCR, and gel electrophoresis to identify the organism and isolate the gene responsible for light production. The main objective was to insert this gene into a bacterial system to confirm its function through observable bioluminescence. However, repeated difficulties in maintaining viable fungal cultures and errors in molecular procedures resulted in inconclusive results, preventing successful gene identification. Due to these …