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Full-Text Articles in Chemistry

Selective Transfection Of A Transferrin Receptor-Expressing Cell Line With Dna-Lipid Nanoparticles And Synthesis Of Parasite-Derived Glycans As Biomarkers For Leishmaniasis, Irodiel Vinales Lozano May 2024

Selective Transfection Of A Transferrin Receptor-Expressing Cell Line With Dna-Lipid Nanoparticles And Synthesis Of Parasite-Derived Glycans As Biomarkers For Leishmaniasis, Irodiel Vinales Lozano

Open Access Theses & Dissertations

Despite notable progress in lipid nanoparticle (LNP)-mediated gene delivery, achieving selective transfection of specific cell types, such as cancer cells, remains a significant hurdle, hindering the advancement of innovative gene therapies. In this study, we engineered an LNP formulation encapsulating plasmid DNA (pDNA) encoding the monomeric Green Lantern (mGL) fluorescent reporter protein. The DT7 peptide ligand targeting human transferrin receptor 1 (hTfR1) was also conjugated to the LNP surface for targeted delivery to hTfR1-expressing cells. Optimization of LNP composition yielded favorable particle diameter, ζ-potential, yield, and pDNA encapsulation efficiency. Evaluation of transfection selectivity using a panel of two engineered cell …


Evidence Of Direct Interaction Between Cisplatin And The Caspase-Cleaved Prostate Apoptosis Response-4 Tumor Suppressor, Krishna K. Raut, Samjhana Pandey, Gyanendra Kharel, Steven M. Pascal Jan 2024

Evidence Of Direct Interaction Between Cisplatin And The Caspase-Cleaved Prostate Apoptosis Response-4 Tumor Suppressor, Krishna K. Raut, Samjhana Pandey, Gyanendra Kharel, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

Prostate apoptosis response-4 (Par-4) tumor suppressor protein has gained attention as a potential therapeutic target owing to its unique ability to selectively induce apoptosis in cancer cells, sensitize them to chemotherapy and radiotherapy, and mitigate drug resistance. It has recently been reported that Par-4 interacts synergistically with cisplatin, a widely used anticancer drug. However, the mechanistic details underlying this relationship remain elusive. In this investigation, we employed an array of biophysical techniques, including circular dichroism spectroscopy, dynamic light scattering, and UV–vis absorption spectroscopy, to characterize the interaction between the active caspase-cleaved Par-4 (cl-Par-4) fragment and cisplatin. Additionally, elemental analysis was …


Structural Insights Into The Cl-Par-4 Protein: Ionic Requirements, Conformational Transitions, And Interaction With Cisplatin, Krishna Kumar Raut Oct 2023

Structural Insights Into The Cl-Par-4 Protein: Ionic Requirements, Conformational Transitions, And Interaction With Cisplatin, Krishna Kumar Raut

Chemistry & Biochemistry Theses & Dissertations

Cancer continues to be the leading global cause of death, with challenges in early diagnosis, drug resistance, non-specific drug targeting, and cancer recurrence and metastasis posing formidable obstacles in cancer therapy. In this context, Prostate Apoptosis Response-4 (Par-4), a pro-apoptotic tumor suppressor protein, emerged as a promising therapeutic target due to its ability to selectively induce apoptosis in cancer cells, thereby minimizing the drug-associated adverse effects. However, a comprehensive understanding of the structural features of Par-4, specifically the caspase-cleaved fragment (cl-Par-4), is crucial for therapeutic advancements.

This dissertation investigated the effects of various ions, both monovalent and divalent, on the …


Synthesis, Radiolabeling And Evaluation Of A Suite Of Tracers With 44Sc For Detecting Extracellular Dna, Zhiyao Li May 2023

Synthesis, Radiolabeling And Evaluation Of A Suite Of Tracers With 44Sc For Detecting Extracellular Dna, Zhiyao Li

McKelvey School of Engineering Theses & Dissertations

Neutrophil extracellular traps involve the rapid translocation of DNA to the outside of the cell under certain stimuli. This structure forms a fibrous network that is able to limit the spread of pathogens and to kill microorganisms. It has also been shown to be present in various pathological processes such as inflammation, autoimmune diseases, and cancer metastasis. Currently, the formation process of NETs in vivo is being extensively studied. However noninvasive detection and quantitation has yet to be achieved. A class of PET tracers are described here that consists of a DNA dye as the backbone that is labeled with …


Sharprazor: Automatic Removal Of Hair And Ruler Marks From Dermoscopy Images, Reda Kasmi, Jason Hagerty, Reagan Harris Young, Norsang Lama, Januka Nepal, Jessica Miinch, William V. Stoecker, R. Joe Stanley Apr 2023

Sharprazor: Automatic Removal Of Hair And Ruler Marks From Dermoscopy Images, Reda Kasmi, Jason Hagerty, Reagan Harris Young, Norsang Lama, Januka Nepal, Jessica Miinch, William V. Stoecker, R. Joe Stanley

Mechanical and Aerospace Engineering Faculty Research & Creative Works

Background: The removal of hair and ruler marks is critical in handcrafted image analysis of dermoscopic skin lesions. No other dermoscopic artifacts cause more problems in segmentation and structure detection. Purpose: The aim of the work is to detect both white and black hair, artifacts and finally inpaint correctly the image. Method: We introduce a new algorithm: SharpRazor, to detect hair and ruler marks and remove them from the image. Our multiple-filter approach detects hairs of varying widths within varying backgrounds, while avoiding detection of vessels and bubbles. The proposed algorithm utilizes grayscale plane modification, hair enhancement, segmentation using tri-directional …


Apkcs Role In Neuroblastoma Cell Signaling Cascades And Implications Of Apkcs Inhibitors As Potential Therapeutics, Sloan Breedy Mar 2023

Apkcs Role In Neuroblastoma Cell Signaling Cascades And Implications Of Apkcs Inhibitors As Potential Therapeutics, Sloan Breedy

USF Tampa Graduate Theses and Dissertations

Neuroblastoma (NB) is a cancer that develops in the neuroblasts. It is the most common cancer in children under the age of 1 year, accounting for approximately 6% of all cancers. The prognosis of NB is linked to both age and degree of cell differentiation. This results in a range of survival rates for patients, with outcomes ranging from recurrence and mortality to high survival rates and tumor regression. Our previous work indicated that PKC-ι promotes cell proliferation in NB cells through the PKC-ι/Cdk7/Cdk2 cascade. We report on two atypical protein kinase inhibitors as potential therapeutic candidates against BE(2)-C and …


Synthesis And Biomedical Applications Of Hollow Iron Oxide Nanoparticles, Aloka S. Paragoda Arachchilage Feb 2023

Synthesis And Biomedical Applications Of Hollow Iron Oxide Nanoparticles, Aloka S. Paragoda Arachchilage

Dissertations, Theses, and Capstone Projects

Nano-scale materials have gained much attention during the past few decades due to the stark differences in their properties compared to bulk material. Thus, they are being studied for a myriad of applications ranging from harnessing solar energy to diagnostics. This thesis focuses on the synthesis of hollow iron oxide nanoparticles using Galvanic replacement reactions and their application in drug delivery. Moreover, the use of a peptide precursor for the enhancement of exosomes is also discussed.

Chapter 1 discusses a simple and economical Galvanic approach used for the synthesis of hollow one-dimensional iron oxide nanotubes. In the initial reaction, the …


Skin Lesion Segmentation In Dermoscopic Images With Noisy Data, Norsang Lama, Jason Hagerty, Anand Nambisan, Ronald Joe Stanley, William Van Stoecker Jan 2023

Skin Lesion Segmentation In Dermoscopic Images With Noisy Data, Norsang Lama, Jason Hagerty, Anand Nambisan, Ronald Joe Stanley, William Van Stoecker

Electrical and Computer Engineering Faculty Research & Creative Works

We Propose a Deep Learning Approach to Segment the Skin Lesion in Dermoscopic Images. the Proposed Network Architecture Uses a Pretrained Efficient Net Model in the Encoder and Squeeze-And-Excitation Residual Structures in the Decoder. We Applied This Approach on the Publicly Available International Skin Imaging Collaboration (ISIC) 2017 Challenge Skin Lesion Segmentation Dataset. This Benchmark Dataset Has Been Widely Used in Previous Studies. We Observed Many Inaccurate or Noisy Ground Truth Labels. to Reduce Noisy Data, We Manually Sorted All Ground Truth Labels into Three Categories — Good, Mildly Noisy, and Noisy Labels. Furthermore, We Investigated the Effect of Such …


Halogen Bonding Interactions Of Haloaromatic Endocrine Disruptors And The Potential For Inhibition Of Iodothyronine Deiodinases, Craig A. Bayse Jan 2023

Halogen Bonding Interactions Of Haloaromatic Endocrine Disruptors And The Potential For Inhibition Of Iodothyronine Deiodinases, Craig A. Bayse

Chemistry & Biochemistry Faculty Publications

Halogen bonding (XB) is a potential mechanism for the inhibition of the thyroid-activating/deactivating iodothyronine deiodinase family of selenoproteins through interactions with halogenated endocrine disrupting compounds (EDCs). Trends in XB interactions were examined using density functional theory for a series of polyhalogenated dibenzo-1,4-dioxins, biphenyls, and other EDCs with methylselenolate, a simple model of the Dio active site selenocysteine. The strengths of the interactions depend upon the halogen (Br>Cl), the degree of substitution, and the position of the acceptor. In terms of donor-acceptor energies, interactions at the meta position are often the strongest, suggesting a link to the topology of THs, …


Ultrasensitive Tapered Optical Fiber Refractive Index, Erem Ujah, Meimei Lai, Gymama Slaughter Jan 2023

Ultrasensitive Tapered Optical Fiber Refractive Index, Erem Ujah, Meimei Lai, Gymama Slaughter

Electrical & Computer Engineering Faculty Publications

Refractive index (RI) sensors are of great interest for label-free optical biosensing. A tapered optical fiber (TOF) RI sensor with micron-sized waist diameters can dramatically enhance sensor sensitivity by reducing the mode volume over a long distance. Here, a simple and fast method is used to fabricate highly sensitive refractive index sensors based on localized surface plasmon resonance (LSPR). Two TOFs (l = 5 mm) with waist diameters of 5 µm and 12 µm demonstrated sensitivity enhancement at λ = 1559 nm for glucose sensing (5-45 wt%) at room temperature. The optical power transmission decreased with increasing glucose concentration due …


Tetrahydrocurcumin Improves Lipopolysaccharide-Induced Myocardial Dysfunction By Inhibiting Oxidative Stress And Inflammation Via Jnk/Erk Signaling Pathway Regulation, Hanzhao Zhu, Liyun Zhang, Hao Jia, Lu Xu, Yu Cao, Mengen Zhai, Kaifeng Li, Lin Xia, Liqing Jiang, Xiang Li, Yenong Zhou, Jincheng Liu, Shiqiang Yu, Weixun Duan Sep 2022

Tetrahydrocurcumin Improves Lipopolysaccharide-Induced Myocardial Dysfunction By Inhibiting Oxidative Stress And Inflammation Via Jnk/Erk Signaling Pathway Regulation, Hanzhao Zhu, Liyun Zhang, Hao Jia, Lu Xu, Yu Cao, Mengen Zhai, Kaifeng Li, Lin Xia, Liqing Jiang, Xiang Li, Yenong Zhou, Jincheng Liu, Shiqiang Yu, Weixun Duan

Chemistry Undergraduate Publications

Background

Acute myocardial dysfunction in patients with sepsis is attributed to oxidative stress, inflammation, and cardiomyocyte loss; however, specific drugs for its prevention are still lacking. Tetrahydrocurcumin (THC) has been proven to contribute to the prevention of various cardiovascular diseases by decreasing oxidative stress and inflammation. This study was performed to investigate the functions and mechanism of action of THC in septic cardiomyopathy.

Methods

After the oral administration of THC (120 mg/kg) for 5 consecutive days, a mouse model of sepsis was established via intraperitoneal lipopolysaccharide (LPS, 10 mg/kg) injection. Following this, cardiac function was assessed, pathological section staining was …


Hepatocellular Carcinoma Image-Guided Intervention: Quantitative Characterization Of Reagents For Thermochemical Ablation, Emily A. Thompson May 2022

Hepatocellular Carcinoma Image-Guided Intervention: Quantitative Characterization Of Reagents For Thermochemical Ablation, Emily A. Thompson

Dissertations & Theses (Open Access)

Thermochemical ablation (TCA) is a minimally invasive therapy under development for hepatocellular carcinoma, a leading cause of cancer death worldwide. TCA utilizes acid-base chemistry delivered simultaneously to induce local ablation when administered. When delivered via a mixing catheter placed directly into the tumor, acid (e.g., AcOH) and base (e.g., NaOH) react to completion at the catheter tip, producing the acetate salt, water, and releasing heat (Δ>50°C) in sufficient quantities to induce lethal osmotic and thermal stress in tumor cells. However, these two reagents are not distinguishable from tissues with noninvasive imaging modalities, which makes monitoring the delivery of TCA …


“Translation Of Hdac6 Pet Imaging Using [18f]Ekz-001 – Cgmp Production And Measurement Of Hdac6 Target Occupancy In Nhps” – A Review, Dania Rahal May 2022

“Translation Of Hdac6 Pet Imaging Using [18f]Ekz-001 – Cgmp Production And Measurement Of Hdac6 Target Occupancy In Nhps” – A Review, Dania Rahal

Chemistry & Biochemistry Undergraduate Honors Theses

The inhibition of histone deacetylase 6 (HDAC6) has been reported to alleviate the effects of neurodegenerative diseases such as Alzheimer’s disease. The brain-penetrant PET radioligand [18F]EKZ-001 has high affinity and selectivity towards HDAC6 and therefore suggests great promise in therapeutic treatment studies and development for neurodegenerative diseases. “Translation of HDAC6 PET imaging using [18F]EKZ-001 – cGMP production and measurement of HDAC6 target occupancy in NHPs” has achieved an effective, fully automated method of producing [18F]EKZ-001 in compliance with current good manufacturing practices (cGMP) to support the translation of [18F]EKZ-001 PET for …


The Effects Of Paclitaxel On Cellular Migration And The Cytoskeleton, Ashley Salguero-Gonzalez Apr 2022

The Effects Of Paclitaxel On Cellular Migration And The Cytoskeleton, Ashley Salguero-Gonzalez

Thinking Matters Symposium

In a clinical setting, some patients are exposed to an anti-cancer chemotherapy agent, paclitaxel. Cancerous cells undergo rapid, continuous cell division without control. Chemotherapy treatments try to slow and stop the uncontrollable cell division cycles and eliminate cancerous cells in the process. Paclitaxel serves as a treatment for some types of cancers, including lung, melanoma, bladder, and esophageal. Because it targets the cytoskeleton, paclitaxel can also influence cell migration. This project utilizes a cellular migration assay and an immunohistochemistry assay to analyze the effects of paclitaxel on the movement of cells and on the cytoskeleton of neuroglia rat cells with …


A Proposed Treatment Of Mixed Connective Tissue Disease By Competitive Inhibition Of Autoantibodies, Thomas Russell Apr 2022

A Proposed Treatment Of Mixed Connective Tissue Disease By Competitive Inhibition Of Autoantibodies, Thomas Russell

Senior Honors Theses

Mixed Connective Tissue Disease is an autoimmune disease characterized by Raynaud’s phenomenon and arthritis among other symptoms. It is primarily caused by antibodies that target the U1-RNP 70K peptide. The treatment proposed in this paper uses competitive inhibition to prevent the binding of the anti-U1-RNP 70K antibodies with the U1-RNP 70K peptide. A method for testing the designed treatment in silico is proposed using AutoDock Vina docking software.


Inflammatory Response To Sleep Fragmentation In Skeletal, Cardiac, And Smooth Muscle Tissues In Female Mice, Patton Allen Jan 2022

Inflammatory Response To Sleep Fragmentation In Skeletal, Cardiac, And Smooth Muscle Tissues In Female Mice, Patton Allen

Mahurin Honors College Capstone Experience/Thesis Projects

Sleep is a critical process that the body undergoes. When sleep is interrupted, so that an individual is awakened for some period before going back into sleep, the sleep can be described as fragmented. Studies in the past have shown that sleep fragmentation (SF) promotes an inflammatory environment, especially in the brain and peripheral tissue. However, studies have not been conducted to observe inflammatory responses in muscle. To examine this, C57BL/6J female mice were subjected to either a control group (no SF) or a SF group which involved using an automated SF chamber to disrupt sleep every 2 min over …


Visualizing Phytochemical-Protein Interaction Networks: Momordica Charantia And Cancer, Yumi L. Briones, Alexander T. Young, Fabian M. Dayrit, Armando Jerome De Jesus, Nina Rosario L. Rojas Dec 2021

Visualizing Phytochemical-Protein Interaction Networks: Momordica Charantia And Cancer, Yumi L. Briones, Alexander T. Young, Fabian M. Dayrit, Armando Jerome De Jesus, Nina Rosario L. Rojas

Chemistry Faculty Publications

The in silico study of medicinal plants is a rapidly growing field. Techniques such as reverse screening and network pharmacology are used to study the complex cellular action of medicinal plants against disease. However, it is difficult to produce a meaningful visualization of phytochemical-protein interactions (PCPIs) in the cell. This study introduces a novel workflow combining various tools to visualize a PCPI network for a medicinal plant against a disease. The five steps are 1) phytochemical compilation, 2) reverse screening, 3) network building, 4) network visualization, and 5) evaluation. The output is a PCPI network that encodes multiple dimensions of …


Lxr Acts As A Differentiator In The Regulation Of Fas And G6pdh Gene Expression Under Insulin Resistant Conditions, Jaafar Hachem Dec 2021

Lxr Acts As A Differentiator In The Regulation Of Fas And G6pdh Gene Expression Under Insulin Resistant Conditions, Jaafar Hachem

Dissertations

Diabetes is a chronic disease that effects 10 percent of the world’s population and causes more than 1.5 million deaths a year and billions of dollars in associated health care cost. It can lead to very serious complications such as renal failure, liver cirrhosis, heart attack, and vision loss. The most common type of diabetes is type 2 diabetes. Type 2 diabetes arises when blood glucose levels remain chronically high due to insulin resistance. The reason for this elevation is due to the failure of insulin to allow tissues to uptake glucose causing problems in subsequent metabolic pathways. Over the …


Statistical Measurements Of Dispersion Measure Fluctuations Of Frbs, Siyao Xu, David H. Weinberg, Bing Zhang Nov 2021

Statistical Measurements Of Dispersion Measure Fluctuations Of Frbs, Siyao Xu, David H. Weinberg, Bing Zhang

Physics & Astronomy Faculty Research

Extragalactic fast radio bursts (FRBs) have large dispersion measures (DMs) and are unique probes of intergalactic electron density fluctuations. By using the recently released First CHIME/FRB Catalog, we reexamined the structure function (SF) of DM fluctuations. It shows a large DM fluctuation similar to that previously reported in Xu & Zhang, but no clear correlation hinting toward large-scale turbulence is reproduced with this larger sample. To suppress the distortion effect from FRB distances and their host DMs, we focus on a subset of CHIME catalog with DM < 500 pc cm-3. A trend of nonconstant SF and nonzero correlation function (CF) at angular separations θ less than 10 is seen, but with large statistical uncertainties. The difference found between SF and that derived from CF at θ ≲ 10 can be ascribed to the large statistical uncertainties or the density inhomogeneities on scales on the order of 100 Mpc. The possible correlation of electron density fluctuations and inhomogeneities of density distribution should be tested when several thousands of FRBs are available.


Aberrant Crosstalk Between Insulin Signaling And Mtor In Young Down Syndrome Individuals Revealed By Neuronal-Derived Extracellular Vesicles, Marzia Perluigi, Anna Picca, Elita Montanari, Riccardo Calvani, Federico Marini, Roberto Matassa, Antonella Tramutola, Alberto Villani, Giuseppe Familiari, Fabio Di Domenico, D. Allan Butterfield, Kenneth J. Oh, Emanuele Marzetti, Diletta Valentini, Eugenio Barone Nov 2021

Aberrant Crosstalk Between Insulin Signaling And Mtor In Young Down Syndrome Individuals Revealed By Neuronal-Derived Extracellular Vesicles, Marzia Perluigi, Anna Picca, Elita Montanari, Riccardo Calvani, Federico Marini, Roberto Matassa, Antonella Tramutola, Alberto Villani, Giuseppe Familiari, Fabio Di Domenico, D. Allan Butterfield, Kenneth J. Oh, Emanuele Marzetti, Diletta Valentini, Eugenio Barone

Chemistry Faculty Publications

INTRODUCTION: Intellectual disability, accelerated aging, and early-onset Alzheimer-like neurodegeneration are key brain pathological features of Down syndrome (DS). Although growing research aims at the identification of molecular pathways underlying the aging trajectory of DS population, data on infants and adolescents with DS are missing.

METHODS: Neuronal-derived extracellular vesicles (nEVs) were isolated form healthy donors (HDs, n = 17) and DS children (n = 18) from 2 to 17 years of age and nEV content was interrogated for markers of insulin/mTOR pathways.

RESULTS: nEVs isolated from DS children were characterized by a significant increase in pIRS1Ser636, a marker of …


Biotinylation As A Tool To Enhance The Uptake Of Small Molecules In Gram-Negative Bacteria, Ankit Pandeya, Ling Yang, Olaniyi Alegun, Chamikara Karunasena, Chad Risko, Zhenyu Li, Yinan Wei Nov 2021

Biotinylation As A Tool To Enhance The Uptake Of Small Molecules In Gram-Negative Bacteria, Ankit Pandeya, Ling Yang, Olaniyi Alegun, Chamikara Karunasena, Chad Risko, Zhenyu Li, Yinan Wei

Chemistry Faculty Publications

Antibiotic resistance is a major public health concern. The shrinking selection of effective antibiotics and lack of new development is making the situation worse. Gram-negative bacteria more specifically pose serious threat because of their double layered cell envelope and effective efflux systems, which is a challenge for drugs to penetrate. One promising approach to breach this barrier is the “Trojan horse strategy”. In this technique, an antibiotic molecule is conjugated with a nutrient molecule that helps the antibiotic to enter the cell through dedicated transporters for the nutrient. Here, we explored the approach using biotin conjugation with a florescent molecule …


Characterization Of Lamellar Liquid Crystal Emulsifiers In Topical Creams Containing A Novel Solvent, Melinda Joanna Sutton Aug 2021

Characterization Of Lamellar Liquid Crystal Emulsifiers In Topical Creams Containing A Novel Solvent, Melinda Joanna Sutton

MSU Graduate Theses

Diethylene glycol monoethyl ether (DEGEE) is a promising solvent component in topical cream formulations due to its superior solubilizing abilities with certain active pharmaceutical ingredients. One of the goals of this study is to characterize the effects of pH on the physical and chemical stabilities of topical cream formulations containing particularly high concentrations of DEGEE by characterizing a full topical pH profile of 3.5 – 9.0. The second goal is to evaluate the presence, amount, and characteristics of lyotropic liquid crystals (LLCs), molecularly structured in a lamellar phase, in a model cream emulsion utilizing polarized light microscopy (PLM). The presence …


Biophysical Characterization Of The Par-4 Tumor Suppressor: Evidence Of Structure Outside The Coiled Coil Domain And Interactions With Platinum Chemotherapeutics, Andrea Megan Clark Apr 2021

Biophysical Characterization Of The Par-4 Tumor Suppressor: Evidence Of Structure Outside The Coiled Coil Domain And Interactions With Platinum Chemotherapeutics, Andrea Megan Clark

Chemistry & Biochemistry Theses & Dissertations

Prostate apoptosis response-4 (Par-4) is an apoptosis-inducing tumor suppressor protein. Full-length Par-4 has previously been shown to be a predominantly intrinsically disordered protein (IDP) under neutral conditions, with significant regular secondary structure evident only within the C-terminal coiled coil domain. However, IDPs can gain ordered structure through the process of induced folding, which often occurs under non-neutral conditions. Previous work has shown that the Par-4 leucine zipper, which is a subset of the C-terminal coiled coil domain, is disordered under neutral conditions, but forms a dimeric coiled coil at acidic pH. Increase in ionic strength was also shown to increase …


The Mechanism Of Β-N-Methylamino-L-Alanine Inhibition Of Trna Aminoacylation And Its Impact On Misincorporation, Nien-Ching Han, Tammy J. Bullwinkle, Kaeli F. Loeb, Kym F. Faull, Kyle Mohler, Jesse Rinehart, Michael Ibba Jan 2021

The Mechanism Of Β-N-Methylamino-L-Alanine Inhibition Of Trna Aminoacylation And Its Impact On Misincorporation, Nien-Ching Han, Tammy J. Bullwinkle, Kaeli F. Loeb, Kym F. Faull, Kyle Mohler, Jesse Rinehart, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

β-N-methylamino-l-alanine (BMAA) is a nonproteinogenic amino acid that has been associated with neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). BMAA has been found in human protein extracts; however, the mechanism by which it enters the proteome is still unclear. It has been suggested that BMAA is misincorporated at serine codons during protein synthesis, but direct evidence of its cotranslational incorporation is currently lacking. Here, using LC-MS–purified BMAA and several biochemical assays, we sought to determine whether any aminoacyl-tRNA synthetase (aaRS) utilizes BMAA as a substrate for aminoacylation. Despite BMAA's previously predicted misincorporation at serine …


Critical And Ictal Phases In Simulated Eeg Signals On A Small-World Network, Louis R. Nemzer, Gary D. Cravens, Robert M. Worth, Francis Motta, Andon Placzek, Victor Castro, Jennie Q. Lou Jan 2021

Critical And Ictal Phases In Simulated Eeg Signals On A Small-World Network, Louis R. Nemzer, Gary D. Cravens, Robert M. Worth, Francis Motta, Andon Placzek, Victor Castro, Jennie Q. Lou

Chemistry and Physics Faculty Articles

Healthy brain function is marked by neuronal network dynamics at or near the critical phase, which separates regimes of instability and stasis. A failure to remain at this critical point can lead to neurological disorders such as epilepsy, which is associated with pathological synchronization of neuronal oscillations. Using full Hodgkin-Huxley (HH) simulations on a Small-World Network, we are able to generate synthetic electroencephalogram (EEG) signals with intervals corresponding to seizure (ictal) or non-seizure (interictal) states that can occur based on the hyperexcitability of the artificial neurons and the strength and topology of the synaptic connections between them. These interictal simulations …


Nebulizer-Based Systems To Improve Pharmaceutical Aerosol Delivery To The Lungs, Benjamin M. Spence Jan 2021

Nebulizer-Based Systems To Improve Pharmaceutical Aerosol Delivery To The Lungs, Benjamin M. Spence

Theses and Dissertations

Combining vibrating mesh nebulizers with additional new technologies leads to substantial improvements in pharmaceutical aerosol delivery to the lungs across therapeutic administration methods. In this dissertation, streamlined components, aerosol administration synchronization, and/or Excipient Enhanced Growth (EEG) technologies were utilized to develop and test several novel devices and aerosol delivery systems. The first focus of this work was to improve the poor delivery efficiency, e.g., 3.6% of nominal dose (Dugernier et al. 2017), of aerosolized medication administration to adult human subjects concurrent with high flow nasal cannula (HFNC) therapy, a form of continuous-flow non-invasive ventilation (NIV). The developed Low-Volume Mixer-Heater (LVMH) …


Nuclear-Targeted Gold Nanoparticles Enhance The Effects Of Radiation Therapy With And Without Liposomal Delivery, Maureen Aliru Dec 2020

Nuclear-Targeted Gold Nanoparticles Enhance The Effects Of Radiation Therapy With And Without Liposomal Delivery, Maureen Aliru

Dissertations & Theses (Open Access)

Less that 10% of pancreatic cancer patients are eligible for curative resection, and clinical trials evaluating chemoradiation in locally advanced patients with unresectable disease have been largely disappointing. New and creative therapeutic approaches are needed to address the unment need for treatment options. The objective of this thesis is to advance radiosensitization of treatment-resistant densely desmoplastic pancreatic cancer using nanoparticles to surmount biological barriers to effective particle distribution for DNA-targeting.

Clinical translation of radiosensitizing nanoparticles has stalled owing to technical challenges. Current strategies to use AuNPs for radiosensitization require large quantities of gold, kilovoltage x-rays, immediate irradiation after intravenous administration, …


Mitochondrial Oxidative And Nitrosative Stress And Alzheimer Disease, D. Allan Butterfield, Debra Boyd-Kimball Sep 2020

Mitochondrial Oxidative And Nitrosative Stress And Alzheimer Disease, D. Allan Butterfield, Debra Boyd-Kimball

Chemistry Faculty Publications

Oxidative and nitrosative stress are widely recognized as critical factors in the pathogenesis and progression of Alzheimer disease (AD) and its earlier stage, amnestic mild cognitive impairment (MCI). A major source of free radicals that lead to oxidative and nitrosative damage is mitochondria. This review paper discusses oxidative and nitrosative stress and markers thereof in the brain, along with redox proteomics, which are techniques that have been pioneered in the Butterfield laboratory. Selected biological alterations in—and oxidative and nitrosative modifications of—mitochondria in AD and MCI and systems of relevance thereof also are presented. The review article concludes with a section …


Mapping Gadolinium Contrast In A Complex Ionic And Photosynthesis Environment Of Pineapple By Near-Infrared And X-Ray Imaging, Subhendra Sarkar, Zoya Vinokur, Chen Xu, Tetiana Soloviova, Amina Shahbaz, Aldona Gjoni Jul 2020

Mapping Gadolinium Contrast In A Complex Ionic And Photosynthesis Environment Of Pineapple By Near-Infrared And X-Ray Imaging, Subhendra Sarkar, Zoya Vinokur, Chen Xu, Tetiana Soloviova, Amina Shahbaz, Aldona Gjoni

Publications and Research

This work explores the diffusivity of a lanthanide complex, Eovist (Gadolinium-Ethoxy Benzyl Diethylenetriamine pentaacetate) that is stable in neutral media but is not in acidic environment. In the current work an acidic fruit model like pineapple that is rich in transition metals was used and a possible transmetallation reaction among Eovist and transition metal complexes was tested using X-ray imaging. Another goal of this work was to perturb the usual and the unusual photosynthesis systems that pineapple has maintained for millions of years during the evolution of circadian genes for efficient water conservation by dark photosynthesis. To detect such photosynthesis …


Synthesis Of Radioluminescent Caf2:Ln Core, Mesoporous Silica Shell Nanoparticles For Use In X-Ray Based Theranostics, Hayden Winter, Megan J. Neufeld, Lydia Makotamo, Conroy Sun, Andrea M. Goforth Jan 2020

Synthesis Of Radioluminescent Caf2:Ln Core, Mesoporous Silica Shell Nanoparticles For Use In X-Ray Based Theranostics, Hayden Winter, Megan J. Neufeld, Lydia Makotamo, Conroy Sun, Andrea M. Goforth

Chemistry Faculty Publications and Presentations

X-ray radiotherapy is a common method of treating cancerous tumors or other malignant lesions. The side effects of this treatment, however, can be deleterious to patient quality of life if critical tissues are affected. To potentially lower the effective doses of radiation and negative side-effects, new classes of nanoparticles are being developed to enhance reactive oxygen species production during irradiation. This report presents the synthesis and radiotherapeutic efficacy evaluation of a new nanoparticle formulation designed for this purpose, composed of a CaF2 core, mesoporous silica shell, and polyethylene glycol coating. The construct was additionally doped with Tb and Eu …