Amino Acids, Peptides, and Proteins Commons^™

Hybridization Kinetics Of Four-Way Junctions Localized On A Dna Scaffold, Katherine N. Taylor

Honors Undergraduate Theses

DNA computing is an ever-growing field with scientists trying to design structures that optimize logic gate communication to develop fast, biologically compatible, computational structures. We hypothesize that by using the principles of DNA computing, it is possible to design a DNA tile capable of studying localized DNA hybridization that can differentiate between oligonucleotides of different structural conformations. This includes synthetically manipulating DNA into a nanostructure that can perform Boolean logic functions to calculate the different rates of hybridization. To test our hypothesis, we designed a DNA Tile that incorporated a 4WJ using YES logic. Linear and hairpin single-stranded (ss) DNA …

Molecular Determinants Of Trp Channel Gating, Briar J. Bell

Theses and Dissertations (ETD)

Transient Receptor Potential (TRP) ion channels are a family of proteins that contribute to a myriad of physiological functions. They have been extensively studied since their discovery 35 years ago; however, there are still many questions regarding the mechanisms by which they function. This family of proteins is characterized by a generally shared structure: an intracellular N terminus featuring ankyrin repeats, six transmembrane helices including the pore domain, a re-entrant loop and TRP helix, and an intracellular C terminus with varying structure. Each of these regions has been implicated in the regular function of TRPs, while mutations that alter trafficking …

Quantum Dots' Toxicity: A Multi-Level Investigation On The Impact Of Quantum Dots On The Actin Cytoskeleton, Nhi Le

Graduate Theses/Dissertations

Quantum dots (QDs) are fluorescence nanomaterials with unique optical and physical properties. As such, they are highly sought after for their potential use in several biomedical and industrial applications. Despite their vast potential, recent studies have suggested that quantum dots are toxic to cells. Yet, the mechanism of quantum dots’ toxicity remains unclear. As such, my thesis aims to comprehensively examine the mechanism of quantum dots’ toxicity, emphasizing how quantum dots disrupt the actin cytoskeleton. In this study, I used RNA sequencing and mass spectrometry to investigate the influence of CdSe/ZnS QDs on the transcriptomic proteomic level of Saccharomyces cerevisiae …

Host-Defense Piscidin Peptides As Antibiotic Adjuvants Against Clostridioides Difficile, Adenrele Oludiran, Areej Malik, Andriana C. Zourou, Yonghan Wu, Steven P. Gross, Albert Siryapon, Asia Poudel, Kwincy Alleyne, Savion Adams, David S. Courson, Myriam L. Cotten, Erin B. Purcell

Chemistry & Biochemistry Faculty Publications

The spore-forming intestinal pathogen Clostridioides difficile causes multidrug resistant infection with a high rate of recurrence after treatment. Piscidins 1 (p1) and 3 (p3), cationic host defense peptides with micromolar cytotoxicity against C. difficile, sensitize C. difficile to clinically relevant antibiotics tested at sublethal concentrations. Both peptides bind to Cu²⁺ using an amino terminal copper and nickel binding motif. Here, we investigate the two peptides in the apo and holo states as antibiotic adjuvants against an epidemic strain of C. difficile. We find that the presence of the peptides leads to lower doses of …

Receptor-Targeted Next-Generation Probiotics Ameliorate Mammalian Colitis, Nicholas L. F. Gallina, Vignesh Nathan, Akshay Krishnakumar, Dongqi Liu, Rishi Drolia, Nicole Irrizary Tardi, Yang Fu, Manalee Samadar, Shivendra Tenguria, Alvin Cai, Ruth Eunice Centeno-Martinez, Timothy A. Johnson, Abigail Cox, Lavanya Reddivari, Bruce Applegate, Xingjian Bai, Luping Xu, Deepti Tanjore, Ramesh Vemulapalli, Rahim Rahimi, Arun K. Bhunia

Biological Sciences Faculty Publications

Introduction: a loss of intestinal barrier function, inflammation, and an elevated expression of epithelial heat shock protein 60 (Hsp60) are features of an inflamed bowel. Probiotics have been used to alleviate colitis-induced pathologies, but offer poor adhesion and adaptation to the diseased gut. We hypothesize that enhancing probiotic adhesion in the inflamed bowel may ameliorate such pathologies. Listeria adhesion protein (LAP; 94-kDa acetaldehyde alcohol dehydrogenase) aids Listeria attachment to the epithelial cells by interacting with the mammalian receptor Hsp60. Bioengineered Lactobacillus casei probiotics (BLPs) expressing LAP showed strong interaction with epithelial Hsp60, a high immunomodulatory response, and sustained epithelial barrier …

Revealing The Elusive Mechanism Of Action Of The Lipid Chaperone Fatty Acid Binding Protein 4, Abdul J. Castillo Ibanez

Theses and Dissertations

Fatty acid binding proteins (FABPs) are pivotal in orchestrating lipid trafficking within cells. This dissertation aims to reveal the mechanism of action of adipocyte FABP (FABP4) by meticulously detailing steps for producing uniformly isotopically labeled protein, understanding dynamics and structural changes in aqueous conditions, analyzing protein-membrane interaction with membrane mimicking models, and revealing its membrane-bound state through novel NMR structural elucidation. Chapter 1 provides an overview of FABP4's indispensable role in lipid trafficking, emphasizing its significance in maintaining cellular homeostasis and metabolic regulation. Chapter 2 delves into the optimization of FABP4 protein expression and proposes a high yield recovery and …

Flexible Fitting Of Alphafold2-Predicted Models To Cryo-Em Density Maps Using Elastic Network Models: A Methodological Affirmation, Maytha Alshammari, Jing He, Willy Wriggers

Computer Science Faculty Publications

Motivation: This study investigates the flexible refinement of AlphaFold2 models against corresponding cryo-electron microscopy (cryo-EM) maps using normal modes derived from elastic network models (ENMs) as basis functions for displacement. AlphaFold2 generally predicts highly accurate structures, but 18 of the 137 models of isolated chains exhibit a TM-score below 0.80. We achieved a significant improvement in four of these deviating structures and used them to systematically optimize the parameters of the ENM motion model.

Results: We successfully refined four AlphaFold2 models with notable discrepancies: lipid-preserved respiratory supercomplex (TM-score increased from 0.52 to 0.69), flagellar L-ring protein (TM-score increased from 0.53 …

Developing Cellular Systems To Elucidate Rna Structural Dynamics Of Cag Expansion Transcripts In Spinocerebellar Ataxias, Victoria Demeo

Electronic Theses & Dissertations (2024 - present)

Spinocerebellar ataxias (SCAs) are a diverse group of over 40 genetically heterogeneous neurodegenerative disorders, many of which are caused by a trinucleotide CAG repeat expansion in the coding region of specific genes. These expansions lead to the production of polyglutamine (polyQ) tracts that interfere with normal protein function, triggering cellular dysfunction and contributing to disease pathogenesis. The most well-known of these SCAs, such as SCA1, SCA2, and SCA3, exhibit progressive neurodegeneration, yet the precise mechanisms through which these mutations cause disease remain poorly understood.

A significant challenge in studying CAG repeat expansion disorders lies in the complexity of the disease …

The Concise Guide To Pharmacology 2023/24: Enzymes, Stephen P. H. Alexander, Doriano Fabbro, Eamonn Kelly, Alistair Mathie, John A. Peters, Emma L. Veale, Jane F. Armstrong, Elena Faccenda, Simon D. Harding, James A. Davies, Stephanie Annett, Detlan Boison, Kathryn Elisa Burns, Carmen Dessauer, Jürg Gertsch, Nuala Ann Helsby, Angela A. Izzo, Rennolds Ostrom, Andreas Papapetropoulos, Nigel J. Pyne, Susan Pyne, Tracy Robson, Roland Seifert, Johannes-Peter Stasch, Csaba Szabo, Mario Van Der Stelt, Albert Van Der Vliet, Val Watts, Szu Shen Wong

Pharmacy Faculty Articles and Research

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the …

The Effects Of Sex Hormones On The Size Of Intestinal Lipoproteins, Andromeda M. Nauli, Ann Phan, Patrick Tso, Surya M. Nauli

Pharmacy Faculty Articles and Research

Larger intestinal lipoproteins are more likely to be retained longer in the intestinal wall, allowing more time for their fat to be hydrolyzed and subsequently taken up by the abdominal viscera. Since men generally accumulate more abdominal visceral fat than women, we sought to determine if males produce larger intestinal lipoproteins compared to females. Using the conscious lymph fistula mouse model, we discovered that the male mice indeed produced larger intestinal lipoproteins than the female mice when they were intraduodenally infused with lipid emulsion. We then employed our differentiated Caco-2 cell model with semipermeable membrane system to determine the effects …

Myod-Skp2 Axis Boosts Tumorigenesis In Fusion Negative Rhabdomyosarcoma By Preventing Differentiation Through P57kip2 Targeting, Silvia Pomella, Matteo Cassandri, Lucrezia D’Archivio, Antonella Porrazzo, Cristina Cossetti, Doris Phelps, Clara Perrone, Michele Pezzella, Antonella Cardinale, Marco Wachtel, Sara Aloisi, David Milewski, Marta Colletti, Prethish Sreenivas, Zoë S. Walters, Giovanni Barillari, Angela Di Giannatale, Giuseppe Maria Milano, Cristiano De Stefanis, Rita Alaggio, Sonia Rodriguez-Rodriguez, Nadia Carlesso, Christopher R. Vakoc, Enrico Velardi, Beat W. Schafer, Ernesto Guccione, Susanne A. Gatz, Lucio Miele

School of Medicine Faculty Publications

Rhabdomyosarcomas (RMS) are pediatric mesenchymal-derived malignancies encompassing PAX3/7-FOXO1 Fusion Positive (FP)-RMS, and Fusion Negative (FN)-RMS with frequent RAS pathway mutations. RMS express the master myogenic transcription factor MYOD that, whilst essential for survival, cannot support differentiation. Here we discover SKP2, an oncogenic E3-ubiquitin ligase, as a critical pro-tumorigenic driver in FN-RMS. We show that SKP2 is overexpressed in RMS through the binding of MYOD to an intronic enhancer. SKP2 in FN-RMS promotes cell cycle progression and prevents differentiation by directly targeting p27Kip1 and p57Kip2, respectively. SKP2 depletion unlocks a partly MYOD-dependent myogenic transcriptional program and strongly affects stemness and tumorigenic …

Elovanoid-N34 Modulates Txnrd1 Key In Protection Against Oxidative Stress-Related Diseases, Jorgelina M. Calandria, Surjyadipta Bhattacharjee, Sayantani Kala-Bhattacharjee, Pranab K. Mukherjee, Yuehan Feng, Jakob Vowinckel, Tobias Treiber, Nicolas G. Bazan

School of Graduate Studies Faculty Publications

The thioredoxin (TXN) system is an NADPH + H+/FAD redox-triggered effector that sustains homeostasis, bioenergetics, detoxifying drug networks, and cell survival in oxidative stress-related diseases. Elovanoid (ELV)-N34 is an endogenously formed lipid mediator in neural cells from omega-3 fatty acid precursors that modulate neuroinflammation and senescence gene programming when reduction-oxidation (redox) homeostasis is disrupted, enhancing cell survival. Limited proteolysis (LiP) screening of human retinal pigment epithelial (RPE) cells identified TXNRD1 isoforms 2, 3, or 5, the reductase of the TXN system, as an intracellular target of ELV-N34. TXNRD1 silencing confirmed that the ELV-N34 target was isoform 2 or 3. This …

Structural Analysis And Activity Correlation Of Amphiphilic Cyclic Antimicrobial Peptides Derived From The [W4R4] Scaffold, Shaima Ahmed El-Mowafi, Anastasia G. Konshina, Eman H. M. Mohammed, Nikolay A. Krylov, Roman G. Efremov, Keykavous Parang

Pharmacy Faculty Articles and Research

In our ongoing quest to design effective antimicrobial peptides (AMPs), this study aimed to elucidate the mechanisms governing cyclic amphiphilic AMPs and their interactions with membranes. The objective was to discern the nature of these interactions and understand how peptide sequence and structure influence antimicrobial activity. We introduced modifications into the established cyclic AMP peptide, [W₄R₄], incorporating an extra aromatic hydrophobic residue (W), a positively charged residue (R), or the unique 2,5-diketopiperazine (DKP). This study systematically explored the structure–activity relationships (SARs) of a series of cyclic peptides derived from the [W₄R₄] scaffold, …

Design Of An Fgf-1-Fgf-2 Heterodimer Variant With Enhanced Stability And Cell Proliferation Activity, Nicholas Alan Pohlman

Chemistry & Biochemistry Undergraduate Honors Theses

The FGF-1 subfamily, composed of FGF-1 and FGF-2, assists in broad health-related processes such as cell proliferation and angiogenesis respectively.^1,2 The subfamily shows promising signs as a therapeutic, however, the inherent thermal instability leads to a low half-life in vivo.³ To assist in improving the stability, FGF-1 and FGF-2 were connected via a 12-residue glycine linker ultimately producing a heterodimer. This heterodimer was further examined to discover its novel properties. Inspiration for this project was drawn from previous research which performed five mutations on FGF-1 ultimately improving stability in the protein complex. In addition to these five …

Improving Estimation Of Coronary Artery Disease Risk Using Haptoglobin Genotyping, Emily Kate Mewborn

Theses and Dissertations (ETD)

Atherosclerotic cardiovascular disease (ASCVD) continues to be the leading cause of death worldwide. While several risk factors contributing to disease progression are well-known, pitfalls and limitations exist for estimating if or when an individual will develop the disease. Coronary artery disease (CAD), a subtype of ASCVD, causes myocardial infarction, contributing to significant morbidity and mortality. Current ASCVD risk estimator calculators lack comprehensiveness and do not include genetic or social determinants of health information, which are known to affect ASCVD risk.

Haptoglobin (Hp) genotype also influences CAD risk. Hp is a protein that binds free hemoglobin released from physiologic or pathologic …

Environmental Exposures And Aging., Daniel Chris Gomes

Electronic Theses and Dissertations

In recent years, research into air pollution has shown that exposure to certain components in air pollution, primarily PM2.5 can accelerate biological aging and thereby lead to increased susceptibility to multiple diseases. We hypothesize that prolonged exposure to air pollutants can result in premature aging leading to extensive tissue dysfunction and susceptibility to diseases. To examine this, we exposed mice to PM2.5 for 9, 15, and 21 days, then measured the telomere lengths, cellular senescence, and histone methylation patterns of multiple cell types. We found consistently increased telomere attrition, cellular senescence and advanced age-consistent histone methylation patterns in groups exposed …

Dietary Analysis For Hashimoto’S Thyroiditis: An Integrative Review, Evan Thompson, Alison Hultquist

Master of Science in Nursing Final Projects

Abstract

Hashimoto’s Thyroiditis (HT) is the leading cause of primary hypothyroidism in the United States. In HT, there is an infiltration by lymphocytes which leads to the production of autoantibodies against the thyroid gland. Throughout this integrative review, the aim was to evaluate the effectiveness of micronutrient supplementation and dietary management as adjunct treatments in HT. The purpose was to assist primary care providers in the development of a more holistic plan of care. Literature published within the past seven years was gathered and reviewed from PubMed, CINAHL, and Cochrane Library. Findings indicate that many patients with HT may benefit …

Prefrontal Cortex Glutamatergic Adaptations In A Mouse Model Of Alcohol Use Disorder, Mahum T. Siddiqi, Dhruba Podder, Amanda R. Pahng, Alexandria C. Athanason, Tali Nadav, Chelsea Cates-Gatto, Max Kreifeldt, Candice Contet, Amanda J. Roberts, Scott Edwards, Marisa Roberto, Florence P. Varodayan

School of Graduate Studies Faculty Publications

Alcohol use disorder (AUD) produces cognitive deficits, indicating a shift in prefrontal cortex (PFC) function. PFC glutamate neurotransmission is mostly mediated by α-amino-3‑hydroxy-5-methyl-4-isoxazolepropionic acid-type ionotropic receptors (AMPARs); however preclinical studies have mostly focused on other receptor subtypes. Here we examined the impact of early withdrawal from chronic ethanol on AMPAR function in the mouse medial PFC (mPFC). Dependent male C57BL/6J mice were generated using the chronic intermittent ethanol vapor-two bottle choice (CIE-2BC) paradigm. Non-dependent mice had access to water and ethanol bottles but did not receive ethanol vapor. Naïve mice had no ethanol exposure. We used patch-clamp electrophysiology to measure …

Regulation Of Protein S Gene Expression By Hypoxia Inducible Factor 1 Α And Estrogen Receptor, Mohammad Mohammad, V. Pilli, M. Kumar, Alaina Guilbeau, Narender Kumar, Rinku Majumder

School of Medicine Faculty Publications

ISTH 2023 Congress June 24-28, 2023, Montreal, Canada

A Novel Function Of Protein S In Clot Retraction, Narender Kumar, Alaina Guilbeau, V. Pilli, Rinku Majumder

School of Medicine Faculty Publications

ISTH 2023 Congress, June 24 - 28, 2023, Montreal, Canada