Macromolecular Substances Commons^™

Exploring Anticholinergic Neurotoxicity: Diphenhydramine's Impact On Neuro-2a Cell Morphology, Expression, And Viability, Jordan B. Mcintyre

Honors Undergraduate Theses

Anticholinergic medications, such as diphenhydramine (commonly known as Benadryl), are increasingly recognized for their association with cognitive impairment and neurodegenerative disease. These medications, which inhibit the action of acetylcholine, a neurotransmitter essential for the formation and utilization of the central and peripheral nervous system, have been implicated in conditions such as dementia and may impact fundamental cellular processes like neurogenesis and cell proliferation. This study investigates the effects of diphenhydramine on neurogenesis when introduced to Neuro-2a cells during differentiation. For all studies cells were plated on coverslips or in 6-well plates with differentiation media containing 0 ng/mL, 50 ng/mL, …

Scalable Biosynthesis And Recovery Of Poly-3-Hydroxybutyrate Produced From Cotton-Derived Glucose By Cupriavidus Necator, Ashley M. Clark, Lucia E. Gargano, Gabriella M. Fioravanti, Hannah M. Schapiro, Ron G. Kander

School of Design and Engineering Papers

To combat the growing issue of petroleum plastic waste, alternative bio-based polymers are being developed. Many of these biopolymers are made from bio-derived materials, or are biodegradable, but the most promising polymers fall in both categories. Polyhydroxyalkanoates (PHAs) are one such class of polymers, and poly-3-hydroxybutyrate (P3HB), the most popular PHA, has shown great potential. This study utilized two types of cotton-derived glucose, alongside commercial glucose, as a feedstock for the biosynthesis of P3HB by Cupriavidus necator (also known as Ralstonia eutropha). The fermentation took place in a 2-L bioreactor, showing potential for scale-up. A single-solvent extraction method was …

In Silico Modelling And Docking Simulation Of Egfr-Targeted Diphtheria Toxin Chimera With Various Targeting Moieties, Muhammad Afif Naufal Bmed, Benedictus Ansell Susanto Bmed, Talitha Dinda Gunawan Bmed, Azhar Ridha Lukman Bmed, Alifa Rahma Rizqina Bmed, Muhammad Misbahul Fuad Bmed

Indonesian Journal of Medical Chemistry and Bioinformatics

Introduction: Cancer is a major etiology of death worldwide due to high mortality and suboptimal medicine. However, an emerging field, targeted therapy enabled a more selective and effective therapeutic action. This article aims to analyze in-silico the hypothetical targeted therapy agent that is combinations of conjugate consisting of EGFR targeting moieties and diphtheria toxin (DT-390).

Method: Our novel peptide is a conjugate of a novel EGFR targeting peptide and DT-390, forming a chimera. The tertiary structure was predicted using AlphaFold 2.0. The best IDDT scoring and stereochemistry profiles were utilized. The HADDOCK2.4 webserver modelled the docking between our …

Methamphetamine-Induced Dna Double-Stranded Breaks: The Impact Of The Dopamine Transporter And Insights Into The Mechanisms Of Dna Damage In Mouse Neuro 2a Cells, Lizette Couto

Dissertations, Theses, and Capstone Projects

Methamphetamine (METH) abuse remains a global health concern, with emerging evidence highlighting its genotoxic potential. In the central nervous system METH enters dopaminergic cells primarily through the dopamine transporter (DAT), which controls the dynamics of dopamine (DA) neurotransmission by driving the reuptake of extracellular DA into the presynaptic neuronal cell. Additional effects of METH on the storage of DA in synaptic vesicles lead to the dysregulated cytosolic accumulation of DA. Previous studies have shown that after METH disrupts intracellular vesicular stores of DA, the excess DA in the cytosol is rapidly oxidized. This generates an abundance of reactive oxygen species …

Nanodiscs: A Novel Approach To The Study Of The Methionine Abc Transporter System, Michael T. Winslow

Master's Theses

Membrane transporter proteins play the vital role of moving compounds in and out of the cell and are essential for all living organisms. ATP Binding Cassette (ABC) family transporters function both as importers and exporters in prokaryotes. MetNI is an E. coli Type I ABC transporter responsible for the uptake of methionine into the cytosol from the cell periplasmic space through the cell membrane to maintain intracellular methionine pools. ABC transporters, like other membrane proteins, are most often mechanistically and structurally studied in vitro, solubilized by detergents. However, detergent micelles may affect the conformational changes of membrane proteins relative to …

Studying The Stability Of Collagen/Heparin Coatings To Be Used In Cell Therapy Applications, Gavin Mussino

Biological Sciences Undergraduate Honors Theses

This honors thesis aims to investigate the reusability and performance of cell coatings for cell therapy applications. Cell therapy, which involves the use of human cells to repair or replace damaged tissues, holds immense potential for medical advancements. However, ensuring the survival and functionality of transplanted cells remains a significant challenge. We focused on studying the effectiveness of coatings applied to cells for improved cell growth and viability. The research project involved the preparation of the coatings using a layer-by-layer method and the subsequent seeding of cells. The coated cells were then subjected to a series of experiments to assess …

Engineered Plga Nanofibers For Drug Delivery, Andrew Mancuso

Dissertations, Theses, and Capstone Projects

Poly-lactic-co-glycolic acid (PLGA) polymers are rapidly gaining momentum as a platform for next-generation drug delivery systems due to their ease and low cost of synthesis, favorable biocompatibility and biodegradability, and lack of toxicity. In particular, the application of drug-loaded PLGA nanofibers directly to a target tissue may represent a promising alternative to traditional routes of drug administration (e.g., oral, injectable) as they offer the potential to greatly improve bioavailability, increase efficacy, and reduce off-target toxicity. Furthermore, the use of such a system may potentially allow for greater flexibility in clinical drug development, by enabling the use of compounds which have …

Nanofabrication For Precision Vaccinology, Karen Zagorski

Theses & Dissertations

Vaccines are among the most effective and safe therapeutics known to mankind. Historically the approach to the creation of new vaccines has been dominated by empirical research, trial, and error. This thesis focuses on the more modern, rational approaches to vaccinology based on the current understanding of the inner workings of the immune system. We used nanotechnology for the generation of novel immunogens, addressed several challenges, and characterized the immune responses.

The preparation, characterization, and troubleshooting of several vaccines against dimeric amyloid beta are covered in chapters 4-6. Despite being ultimately unsuccessful, this part provided a deeper understanding of the …

Structural And Biochemical Studies Of Three Enzymes Involved In Amino Acid Metabolism To Develop Novel Drugs, Yahani Pankaja Jayasinghe Arachchige

Theses & Dissertations

Intrinsic drug resistance in bacteria predates the clinical use of antibiotics. Additionally, heterogeneous metabolic states and the ability of many bacteria to form biofilms further enhances bacterial survival during infection and exacerbates treatment challenges. This necessitates the identification of novel drugs against new drug targets. These studies focus on the development of compounds targeting enzymes in Mycobacterium tuberculosis (Mtb) and Staphylococcus aureus that avoid intrinsic antibiotic defenses. The Mtb-encoded homoserine transacetylase enzyme (HTA) catalyzes the first step of the methionine biosynthesis pathway that produces methionine and S-adenosyl methionine. These compounds are shown to be essential for both dormant …

Molecular Dynamics Simulations Of Self-Assemblies In Nature And Nanotechnology, Phu Khanh Tang

Dissertations, Theses, and Capstone Projects

Nature usually divides complex systems into smaller building blocks specializing in a few tasks since one entity cannot achieve everything. Therefore, self-assembly is a robust tool exploited by Nature to build hierarchical systems that accomplish unique functions. The cell membrane distinguishes itself as an example of Nature’s self-assembly, defining and protecting the cell. By mimicking Nature’s designs using synthetically designed self-assemblies, researchers with advanced nanotechnological comprehension can manipulate these synthetic self-assemblies to improve many aspects of modern medicine and materials science. Understanding the competing underlying molecular interactions in self-assembly is always of interest to the academic scientific community and industry. …

Anatomy And Physiology Preparatory Course Textbook (2nd Edition), Carlos Liachovitzky

Open Educational Resources

The goal of this preparatory textbook is to give students a chance to become familiar with some terms and some basic concepts they will find later on in the Anatomy and Physiology course, especially during the first few weeks of the course.

Organization and functioning of the human organism are generally presented starting from the simplest building blocks, and then moving into levels of increasing complexity. This textbook follows the same presentation. It begins introducing the concept of homeostasis, then covers the chemical level, and later on a basic introduction to cellular level, organ level, and organ system level. This …

Biochemical Characterization Of Small Molecule Inhibitor Binding On A Ras Related Gtpase And Its Effector Interactions, Djamali Muhoza

Graduate Theses and Dissertations

The Ras superfamily of GTPases has 167 proteins that are involved in various cellular processes such as proliferation, transformation, migration, and inhibition of cell death. Mutations, abnormal expression, and function of these proteins are observed in many diseases, including several forms of cancer. Even though these GTPases were among the first discovered oncogenes, no successful Ras drug candidate has successfully passed clinical trials. Drugs targeting these proteins have failed mainly because of the complexity of their regulation, their high affinity to GTP, and their structure’s dynamic nature. Recently, novel promising targeting approaches have renewed interest in the Ras drug discovery …

Applied Molecular Dynamics: From Targeting Viral Helicases, To Understanding The Interactions Of Cucurbituril Complexes In Ionic Solutions, Bryan Raubenolt

LSU New Orleans Theses and Dissertations

Molecular Dynamics simulations are a highly useful tool in helping understand the fundamental interactions present in a variety of chemical systems. The work discussed here illustrates it’s use in determining the conformational dynamics of the Zika and SARS-Cov-2 helicase in a physiological environment, largely in an effort to discover inhibitors capable of rendering the protein inert. Additionally, we show how it can be used to understand paradoxical trends in the anion-induced precipitation of Cucurbituril cavitands.

Viral helicases are motor proteins tasked with unwinding the viral dsRNA, a crucial step in preparing the strand to be translatable by host cells. By …

Determining The Link Between Advanced Glycation Endproducts (Ages), Feeding, And Metabolism, Lauren Wimer

Natural Sciences and Mathematics | Biological Sciences Master's Theses

Reactive a-dicarbonyls (a-DC’s), such as methylglyoxal (MGO), are unavoidable metabolites generated during glycolysis that accumulate with age and have been linked with chronic age-related metabolic diseases such as Diabetes Mellitus. Diabetes Mellitus is generally characterized by peripheral neuropathy and sustained hyperglycemia. Chronic hyperglycemia leads to an increase in glycolysis and a downstream increase in reactive a-DC’s. The human body has a natural method of detoxifying these a-DC’s. Glycolytic cells have enzymes which can detoxify a-DC’s, but if overwhelmed, a-DC’s can accumulate and react non-enzymatically with proteins, lipids and DNA to yield a group of molecules called advanced glycation end-products (AGEs). …

‘Am I Turning Into A Man?’ Experiences Of Pakistani Women With Pcos, Rida E Zehra Zaidi

MSJ Capstone Projects

According to the National Institutes of Health, 20 – 25% of all regularly ovulating women have PCOS. This disorder has a range of visible symptoms including excessive weight gain, hirsutism, acne, and hair loss among others. These symptoms make it difficult for women with the syndrome to fit the femininity ideals of the society, as it demands female bodies to be slim, smart, hair less, and to have porcelain skin and regular menstrual cycles. Women with PCOS and other health problems in Pakistan spend all their lives fighting unnecessary battles. This struggle has severe impacts on their physical and mental …

Developing A Dissociative Nanocontainer For Peptide Drug Delivery, Michael Patrick Kelly

Dissertations, Theses, and Capstone Projects

The potency and specificity of bioactive peptides have propelled these agents to the forefront of pharmacological research. However, delivery of peptides to their molecular target in cells is a major obstacle to their widespread application. A Trojan Horse strategy of packaging a bioactive peptide within a modified protein cage to protect it during transport, and releasing it at the target site, is a promising delivery method. Recent work has demonstrated that the viral capsid of the P22 bacteriophage can be loaded with an arbitrary, genetically-encoded peptide, and externally decorated with a cell-penetrating peptide, such as HIV-Tat, to translocate across in …

Isolation, Analysis, And Partial Characterization Of An Inhibitor Of Neisseria Gonorrhoeae, Natania Paul

Undergraduate Honors Theses

There is an emerging threat of Neisseria gonorrhoeae strains that are resistant to all antibiotics. Because of this, the purpose of this research is to isolate, analyze, and partially characterize a new inhibitor(s) of N. gonorrhoeae. Since there is an unknown molecule secreted by Candida albicans that inhibits N. gonorrhoeae, this molecule can be partially characterized using ¹H NMR Spectroscopy to assist in the development of a new antibiotic compound. It was hypothesized that quorum-sensing molecules, trans, trans- farnesol, tyrosol, phenylethyl alcohol, and tryptophol, could be possible candidates for the inhibitor. Because of this, ¹H …

Development Of A Lectin-Fc Fusion Protein With Antiviral And Anti-Cancer Activity., Matthew William Dent

Electronic Theses and Dissertations

This thesis describes the development of a novel lectin-Fc fusion protein and its antiviral and anti-cancer activity. The molecule, Avaren-Fc (AvFc), is a fusion of a variant of the actinomycete lectin actinohivin (Avaren) and the Fc region of human IgG1, and is selective for the terminal α1,2-mannose residues found at the ends of high-mannose-type glycans that can be found on the surface of certain heavily glycosylated viruses and cancer cells. Here, AvFc was found to be able to neutralize simian immunodeficiency virus as well as Hepatitis C virus with nanomolar IC₅₀ values. Furthermore, AvFc recognizes a number of cell …

The First In Vivo Human Methionine Sulfide Proteome And The Impact Of Smoking, Abdullah Qassab

Graduate Theses and Dissertations

Reactive oxygen species are naturally generated within the human body and they are known to modulate signaling pathway and mediate other physiological activities. However, excessive generation of ROS and the inability of body defense system in detoxifying them results in the so called “oxidative stress”. Methionine has powerful antioxidant properties due to the presence of electronegative sulfur in its structure. Therefore, Met is readily oxidized, and methionine sulfoxide has been linked to several pathological conditions.

The urinary proteome is an attractive candidate for the discovery of biomarkers to diagnose and classify health conditions because of the non-invasive collection procedure. However, …

Development And Preclinical Evaluation Of Long-Lasting Cocaine Hydrolases For Cocaine Overdose And Cocaine Use Disorder Treatment, Ting Zhang

Theses and Dissertations--Pharmacy

Cocaine is a plant-based illicit drug commonly involved in substance use disorder. Although cocaine overdose and cocaine use disorders cause adverse health consequences to individuals and the economic burden on their family and society, there are no FDA (Food and Drug Administration) approved medications for treatment. Recently, it has been recognized that delivery of cocaine hydrolase (CocH) is a promising therapeutic strategy. Human butyrylcholinesterase (hBChE), the primary enzyme involved in cocaine metabolism in human, have advantages over other candidates for the development of CocH. Previous studies in our laboratory have designed and characterized hBChE mutants that have ~4,000-fold improved catalytic …

Diversity Oriented Synthesis, Characterization And Anti-Cancer Activity Of Killer Peptide Nucleolipid Bioconjugates, Niki K. Rana

Seton Hall University Dissertations and Theses (ETDs)

The killer peptide sequence D-(KLAKLAK)₂ has been originally designed and developed as an antibacterial agent. Despite having excellent cytotoxicity towards bacteria, this sequence maintains low cell cytotoxity in malignant mammalian cell types such as cancer. The chemical basis for its selectivity has been attributed to its poly(cationic) amphiphilic nature, which facilitates cell permeability across the negatively charged bacterial membrane, but with limited permeability across the zwitterionic membrane of mammalian cells. The positively charged D-(KLAKLAK)₂ sequence has been found to accumulate on the surface of the mitochondria causing dissipation of the negatively charged mitochondrial membrane potential. This charge disruption …