Biochemistry, Biophysics, and Structural Biology Commons^™

Integrating In Vitro And In Silico Approaches To Gain Insight Into The Mechanism Of Amyloid Fibrillogenesis, Marvin M. Bilog

Dissertations, Theses, and Capstone Projects

Amyloid fibril formation, the hallmark of numerous amyloid-related diseases, has been the subject of a vast number of scientific studies due to its pathological implications. Since the fibrillization process exhibits a certain level of intricacy, its investigation requires a multidisciplinary approach that integrates both experimental and computational methods. In vitro techniques involve biophysical assays and imaging tools for characterizing the structural and kinetic aspects of amyloid fibril formation. In parallel, in silico techniques offer programs for predicting atomistic details and behaviors of amyloidogenic proteins and peptides at the nanoscale level. Serum amyloid A (SAA), human islet amyloid polypeptide (hIAPP), and …

Positron Emission Tomography In Oncology And Environmental Science, Samantha Delaney

Dissertations, Theses, and Capstone Projects

The last half century has played witness to the onset of molecular imaging for the clinical assessment of physiological targets. While several medical imaging modalities allow for the visualization of the functional and anatomical properties of humans and living systems, few offer accurate quantitation and the ability to detect biochemical processes with low-administered drug mass doses. This limits how physicians and scientists may diagnose and treat medical issues, such as cancer, disease, and foreign agents.

A promising alternative to extant invasive procedures and suboptimal imaging modalities to assess the nature of a biological environment is the use of positron emission …

Towards A New Role Of Mitochondrial Hydrogen Peroxide In Synaptic Function, Cliyahnelle Z. Alexander

Student Theses and Dissertations

Aerobic metabolism is known to generate damaging ROS, particularly hydrogen peroxide. Reactive oxygen species (ROS) are highly reactive molecules containing oxygen that have the potential to cause damage to cells and tissues in the body. ROS are highly reactive atoms or molecules that rapidly interact with other molecules within a cell. Intracellular accumulation can result in oxidative damage, dysfunction, and cell death. Due to the limitations of H₂O₂ (hydrogen peroxide) detectors, other impacts of ROS exposure may have been missed. HyPer7, a genetically encoded sensor, measures hydrogen peroxide emissions precisely and sensitively, even at sublethal levels, during …

Exploring The Design Space Of Antifungal Peptides, Miryam Kikhwa

Seton Hall University Dissertations and Theses (ETDs)

The synthesis, characterization, and evaluation of antifungal activity of peptides FQ15 and FG10 will be conducted to address the hypothesis. The hypothesis of this thesis is that a peptide with similar properties to AS15 would have similar activity against Cryptococcus neoformans. This study addresses the challenge of drug- resistant microbes by developing inhibitors targeting lipid flippase and exploring their potential as antimicrobial agents against Cryptococcus neoformans. Chapter 1 provides a historical context of the background on the development of antimicrobials and common antifungal treatments, as well as an introduction about C. neoformans and its resistance mechanism. Chapter 2 introduces the …

Assessing The Pre- And Post-Synaptic Effects Of Opioids On Inspiratory Rhythmogenesis, Jingzhi Zhao, Diego Morandi Zerpa

Biology and Medicine Through Mathematics Conference

No abstract provided.

Purification Of Recombinant E. Coli Topoisomerase Iii For Structure-Based Drug Design Using Protein Crystallization, Miguel A. Perez Rodriguez, Yuk-Ching Tse-Dinh

FIU Undergraduate Research Journal

Type IA Topoisomerases are ubiquitous enzymes found throughout all life forms and species. These topoisomerases relieve the topographical constrains formed by DNA during processes like replication and transcription via a cleavage-religation mechanism performed through a catalytically active tyrosine residue in the primary structure of the enzyme. E. coli Topoisomerase III (EtopIII) is a type of Type IA topoisomerase, and its main function in the cell is as a decatenase, which means that it unlinks circular or intertwined pieces of genetic material and creates two unlinked segments of DNA from a singular linked chain. Structure-based determination of the enzyme’s three-dimensional structure …

The Evolution Of Tumor Suppressing Genes In Multicellular Organisms: Nature’S Prevention Of Oncogenesis, Melanie Perez

FIU Undergraduate Research Journal

The p53 gene family, a well-known group of genes, is the primary propagator of tumor-suppressing mechanisms in multicellular organisms. Although they are currently critical drug targets in cancer, the p53 family also serves specific functions in the development of multicellular organisms. In this paper, the current function, origin, and evolutionary purpose of the p53 family are reviewed in the evolution of multicellular organisms. The TP53 gene induces cellular responses such as apoptosis as a way to combat detrimental environmental and cellular factors that can damage the integrity of a cell’s DNA. The other two members of the p53 family are …

Assay Replicability In Β-Glucosidase Enzyme Kinetics Across Laboratories, Nicole-Tia Najam, Jaime Mayoral

FIU Undergraduate Research Journal

Replicability is the foundation of research in any scientific discipline. Despite this fact, few studies address experimental variability within and across multiple institutions that operate under the same protocol. While consistency is usually well documented within the same lab, multi-institutional experiments may introduce new variables and, therefore, variability that may lead to inconsistent results. This study seeks to explore intra- and interinstitutional variability among enzyme catalytic efficiency values (K_M and K_cat/K_M) for the wild type of β-Glucosidase derived from Paenibacillus polymyxa. A standardized protocol for the assay was provided to all institutions that participated in …

The Interactions Of Centromeric Nucleosomes Elucidated By Atomic Force Microscopy, Shaun Filliaux

Theses & Dissertations

Nucleosomes are the fundamental unit of compaction for DNA in the genome. These positively charged proteins have two main types of nucleosomes: canonical (H3 containing) and centromere (CENP-A containing). The compacting of DNA allows for DNA to fit into the nucleus of cells, but creates a barrier for DNA accessibility for operations such as replication or transcription. Centromeric chromatin is a subset of chromatin structure and governs chromosome segregation. Compared to the bulk chromosome, centromeres are composed of H3 and CENP-A nucleosomes in which H3 histones is replaced by its homolog CENP-A histone. This results in nucleosomes with different structures, …

The Role Of Med13 In Proteaphagy, John Sauer, Brittany Friedson, Katrina Cooper

Rowan-Virtua Research Day

Regulation of proteasomes is important for adaptation to cellular stress. Previous studies have shown that following starvation stress, proteasomes are targeted for destruction by autophagy. However, how cells control proteasomes in response to nitrogen starvation remains unclear. This study delves into the intricate interplay between Med13, proteaphagy, and stress response regulation, aiming to elucidate their roles in cellular survival mechanisms. It focused on the highly conserved Cdk8 kinase module (CKM) of the Mediator complex a that plays a pivotal involvement in cellular signaling and gene regulation under stress conditions. During the investigation, we asked if the degradation of specific proteasome …

Characterizing The Role Of Pa5189 Of Pseudomonas Aeruginosa In Deletion And Overexpression Mutants, Seh Na Mellick

Theses/Capstones/Creative Projects

In the context of rising multidrug resistance in biofilm-forming pathogens like Pseudomonas aeruginosa, this study investigates the role of the understudied transcription factor PA5189 in antibiotic resistance and biofilm formation. PA5189 deletion and overexpression mutants were created in a parent P. aeruginosa strain using pEX18Tc-based recombinant suicide vectors, with genotypic verification of putative triparental conjugants achieved through restriction digestion and PCR. The study revealed that PA5189 overexpression significantly increases resistance to commonly used broad spectrum antibiotics such as ciprofloxacin and imipenem. Additionally, differential expression of PA5189 was found to notably affect biofilm formation, with variations contingent on the nutrient …

Establishing An Objective, Quantifiable Method For Detecting Erosive Tooth Wear, Camille Kita

Biological Sciences Undergraduate Honors Theses

This study aims to monitor and evaluate erosive tooth wear (ETW) by measurement of enamel surface thickness and texture in a clinical setting. The objective approach is fundamentally different from the standard subjective visual assessment that professionals in the dental field using the Basic Erosive Wear Evaluation (BEWE) method.

Twenty-nine hyposalivation and three control subjects were used in this longitudinal study, for a total of 597 samples (only 577 teeth were eligible for surface texture analysis) evaluated in a longitudinal study including both baseline and 12 month follow up surfaces. Each participant’s buccal surface of the tooth was first analyzed …

Cyanoacrylate Deposition Onto Sebum With Pretreatment Of Amine, Isaac Baltz

Chemistry & Biochemistry Undergraduate Honors Theses

Super glue, or ethyl cyanoacrylate, fuming is commonly used in forensic science to develop latent fingerprints on nonporous surfaces[7]. Fingerprints are primarily made up of the oily substance secreted by sebaceous glands better known as sebum. Previously it has been shown that exposure of fingerprints to diisopropylamine dramatically increases the deposition of cyanoacrylate polymers on the fingerprints[1]. However, the heterogeneity of any series of real fingerprints made it difficult to quantitatively assess this effect. This heterogeneity includes not just the amount of sebum but the presence of unknown amounts of proteins, amino acids, and other potential nucleophiles which catalyze the …

Model-Based Comparison Of Biological Organism And Electro-Mechanical System Resiliency Strategies, Nicholas Ratycz

Mechanical Engineering Undergraduate Honors Theses

Bio-inspired design has been used by many engineers to solve difficult problems or to make manufacturing processes more efficient. Biomimetics is the study of implementing the structure or function of biological substances, materials, mechanisms, and processes onto artificial ones that mimic the original. The goal of the BIASD tool is to provide bio-inspiration for engineers by studying the fault-adaptive strategies that biological systems use, rather than just their structure or function. In this thesis, the fault adaptive strategies of both a biological example and that of a real cubesat are compared using three types of model-based system diagrams to show …

A Review Of Rheb Activation Of Mtorc1 And The Great Mystery Of One Missing Gef, Jack Gregory

Senior Honors Theses

The mTORC1 pathway is involved in the regulation of cell growth and translation. The pathway has a complex web of activators and inhibitors to activate mTORC1. mTORC1 is regulated via a small GTPase called Rheb, which interacts directly with mTORC1. This GTPase and its GTPase activating protein (GAP), TSC1/2, have been widely studied to understand how the variety of regulators of mTORC1 interact with these proteins. Despite this, the guanine nucleotide exchange factor (GEF) of Rheb has yet to be identified. This review broadly analyzes Rheb and mTORC1, their structures, regulations, and interactions, and explores the mystery of the missing …

College Of Natural Sciences Newsletter, Spring 2024, College Of Natural Sciences

College of Natural Sciences Newsletters and Reports

Page 1 Dean's Message
Page 2 New Faculty and New Club on Campus
Page 3 2024 URSCAD Awards
Page 4 Day of Scholars 2024
Page 5 SDSU's First Representation at the Association for Anatomy's 2024
Annual Conference
Page 6-7 2024 Honor's College Convocation
Page 8 Other Student Activities
Page 9 Faculty Awards
Page 10-11 Other News
Page 12 2024 Drone Day and American Association of Geographers Convention - Hawaii
Page 13 55th Annual Geography Convention
Page 14 2024 Stethoscope Ceremony
Page 15 Open PRAIRIE Data

Understanding Taf13 (Tata Box-Binding Protein-Associated Factor 13) Upregulation In Eukaryotic Cells, Selin Kaplanoglu

Honors Theses

TATA-binding protein (TBP) and TBP-associated factors (Tafs) comprise RNA Polymerase II (RNA Pol II) pre-initiation complex. This universal component carefully controls the transcriptional initiation process. One of the Tafs, Taf13, also plays an important role in the regulation of RNA Pol II transcription initiation which is evolutionarily conserved from yeast to humans. It is found that Taf13 is overexpressed in cancer cells, although the exact mechanism that is responsible for this overexpression is unclear. Our hypothesis suggests that targeted degradation by the 26S proteasome via ubiquitylation [Ubiquitin-Proteasome System (UPS)] may be the mechanism that regulates the stability of Taf13. To …

Molecular Characterization Of Stress Response In Western Honey Bee (Apis Mellifera), Faizan Tahir

Master's Theses

Honey bees are incredibly important for the reproduction of flowering plants and the sustainability of agricultural ecosystems. However, they face various stressors such as pesticides, pathogens, habitat loss, and climate change. Extensive research has been conducted to understand how bees respond to these stressors. Scientists have discovered that honey bees exhibit complex physiological and behavioral responses to stress at individual and colony levels. Stress can have a significant impact on their immune function, foraging behavior, and reproductive success (Decourtye et al., 2010). Understanding bee responses to stress is crucial for several reasons. Firstly, honey bees are vital for the pollination …

Identifying A Target Protein And Ligands For Autoimmune Disorders, Sarah Caruthers

Computational and Data Sciences (MS) Theses

Systemic Lupus Erythematosus (SLE) is an autoimmune disorder characterized by unprovoked inflammatory responses that lead to tissue degradation. Patients suffering from SLE display an overexpression of master regulatory protein HIF-1 HIF-1is a transcription factor for pro-inflammatory cytokine interleukin-17A (IL-17A), which is highly involved in inflammatory reactions within the body. To search for a treatment for SLE, computer aided drug discovery techniques were utilized. The transcription factor complex for IL-17A was reconstructed through multiple protein docking techniques. The heteroprotein complex was profiled using 3D macromolecular visualization software and binding cavities within HIF-1 were calculated. Molecular docking simulations were run on the …

Pipecolic Acid And Novel Insights Into Cerebral Malaria, Akua E. Mensah

Theses

Cerebral malaria (CM), a severe manifestation of Plasmodium infection, prompts our investigation into the nuanced role of pipecolic acid in its pathophysiology. To unravel the molecular intricacies, we conducted in vitro lysine labeling techniques of mice infected with P. berghei ANKA parasites, and human P. falciparum grown in vitro, aiming to discern the impact of Plasmodium on pipecolic acid production. Previous observations indicated an elevation in pipecolic acid levels correlating with neurological decline in children with CM. In our study, confirming elevated pipecolic acid presence in the plasma and brain tissues of CM patients and the animal model of CM, …

A Combination Of Generated Hydrogen Sulfide And Nitric Oxide Activity Has A Potentiated Protectant Effect Against Cisplatin Induced Nephrotoxicity, Faria Khurshid, Javeid Iqbal, Fiaz Ud Din Ahmad, Arslan Hussain Lodhi, Abdul Malik, Suhail Akhtar, Azmat Ali Khan, Marvi Imam Bux, Mohammed Younis

Biomedical Sciences Faculty Publications

Aim: Hydrogen sulfide and nitricoxide possess cytoprotective activity and in vivo, they are generated from exogenous sodium hydrosulfide and L-arginine respectively. Cisplatin is a major chemotherapeutic agent used to treat cancer and has a high incidence of nephrotoxicity as a side effect. The study aim was to explore the effects of NaHS and L-arginine or their combination on cisplatin induced nephrotoxicity in rats. Methods: Wistar Kyoto rats were given a single intraperitoneal dose of cisplatin (5 mg/kg) followed either by NaHS (56 μmol/kg, i. p.), L-arginine (1.25 g/L in drinking water) or their combination daily for 28-days. Post-mortem plasma, urine …

The Purification And Thermal Stability Of The Peroxidase Enzyme In Cucurbita Moschata, Garen Hamner

Senior Honors Theses

Peroxidases are enzymes that catalyze the reduction of hydrogen peroxide to water while oxidizing organic substrates and are valuable in spheres like industrial and medical applications and histochemistry. Limitations still exist in the use of the well-studied horseradish peroxidase for certain activities due to limitations like poor thermal stability, thus the search for novel peroxidases that can overcome these limitations is an active area of research. Butternut squash peroxidase (Cucurbita moschata) (BSP) shows promise due to significant activity being found in the skin and apparent enhanced thermal stability, but an efficient purification scheme for it is lacking, as well as …

Using Edna To Assess Impacts Of Oyster Restoration On Ecosystem Biodiversity At A Heavily Impacted Coastal Lagoon, Dominique Di Domenico, Emily Bonacchi, Elizabeth Suter

Molloy Multidisciplinary Undergraduate Research Conference

The Great South Bay (GSB), a bar-built, temperate, coastal lagoon on the south shore of Long Island, New York, USA, is a highly modified estuary due to heavy urbanization and suburbanization in the last century. GSB historically provided up to 50% of the nation’s hard clam (Mercenaria mercenaria) harvest, and is the legal home of the “Blue Point” oyster (eastern oyster; Crassostrea virginica). However, due to overexploitation as well as persistent stress from ongoing nitrogen pollution and harmful algal blooms, shellfish populations are fractions of their original abundances. Restoration efforts in GSB, driven both by community efforts …

Trna Anticodon Cleavage By Target-Activated Crispr-Cas13a Effector, Ishita Jain, Matvey Kolesnik, Konstantin Kuznedelov, Leonid Minakhin, Natalia Morozova, Anna Shiriaeva, Alexandr Kirillov, Sofia Medvedeva, Alexei Livenskyi, Laura Kazieva, Kira S Makarova, Eugene V Koonin, Sergei Borukhov, Konstantin Severinov, Ekaterina Semenova

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Type VI CRISPR-Cas systems are among the few CRISPR varieties that target exclusively RNA. The CRISPR RNA–guided, sequence-specific binding of target RNAs, such as phage transcripts, activates the type VI effector, Cas13. Once activated, Cas13 causes collateral RNA cleavage, which induces bacterial cell dormancy, thus protecting the host population from the phage spread. We show here that the principal form of collateral RNA degradation elicited by Leptotrichia shahii Cas13a expressed in Escherichia coli cells is the cleavage of anticodons in a subset of transfer RNAs (tRNAs) with uridine-rich anticodons. This tRNA cleavage is accompanied by inhibition of protein synthesis, thus …

Investigating The Role Of Tryptophan In The Native Photo-Crosslinking Of A Cys-Containing Transmembrane Helix To A Membrane Lipid Double Bond, Michael Jay Telehany

Undergraduate Honors Theses

Our research group has previously discovered that a Cys residue within a transmembrane (TM) helix can directly photo-crosslink to a membrane lipid via an oxythiolation addition reaction to the double bond within the lipid, with a reaction yield of 10-20%. The pH-low Insertion Peptide (pHLIP) serves as our model TM helix, while the POPC lipid bilayer is our model membrane. We had long believed that the Trp residues within the sequence of pHLIP served as the key chromophore for this reaction, and thus they were essential for the formation of the TM helix-lipid adduct. To test this hypothesis, I synthesized …

Predictive And Prognostic Biomarkers And Tumor Antigens For Targeted Therapy In Urothelial Carcinoma, Aditya Eturi, Amman Bhasin, Kevin Zarrabi, William Tester

Department of Medical Oncology Faculty Papers

Urothelial carcinoma (UC) is the fourth most prevalent cancer amongst males worldwide. While patients with non-muscle-invasive disease have a favorable prognosis, 25% of UC patients present with locally advanced disease which is associated with a 10-15% 5-year survival rate and poor overall prognosis. Muscle-invasive bladder cancer (MIBC) is associated with about 50% 5 year survival when treated by radical cystectomy or trimodality therapy; stage IV disease is associated with 10-15% 5 year survival. Current therapeutic modalities for MIBC include neoadjuvant chemotherapy, surgery and/or chemoradiation, although patients with relapsed or refractory disease have a poor prognosis. However, the rapid success of …

Isolation And Analysis Of R130d Malate Dehydrogenase (Mdh), Hayley Brunette, Abby Doyle, Ilsa Hoaglund, Danielle Bolland

Undergraduate Research Symposium 2024

Malate Dehydrogenase (MDH) is the enzyme that catalyzes the ninth step of the citric acid cycle, a regenerative step in the metabolism of glucose in which malate is converted to oxaloacetate. Conformational changes in the active loop region of MDH along with the coenzyme NAD+ drive catalysis. Previous studies suggested that mutating positively charged amino acids to negatively charged amino acids at residue 130 decreased the enzymatic activity of MDH. We hypothesized that if we change arginine 130 (positively charged amino acid) to aspartate (negatively charged amino acid), then the enzymatic activity of MDH would significantly decrease. In e. Coli …

Upregulation Of The Predominant Cystic Fibrosis Causing Mutation Df508-Cftr By Triazole Compounds In Epithelial Cells, Maggie Taylor

Undergraduate Research Conference

Cystic fibrosis is a common genetic disease that is caused by a mutation in the plasma membrane protein CFTR, which stands for Cystic Fibrosis Transmembrane-conductance Regulator. When this membrane protein is mutated, it impairs its chloride ion channel function, blocking the movement of chloride ions that travel in and out of the cell. Previous studies have demonstrated that the most prevalent CFTR mutation, ∆F508-CFTR, can be partially reversed using small molecules (Heda and Marino, BBRC, 271:659-664, 2000). In this study, I have investigated the effects of several triazole compounds known to bind and transport chloride ions in cultured cells, on …

Hgs-3 The Influence Of A Tandem Cycling Program In The Community On Physical And Functional Health, Therapeutic Bonds, And Quality Of Life For Individuals And Care Partners Coping With Parkinson’S Disease, Leila Djerdjour, Jennifer L. Trilk

SC Upstate Research Symposium

Purpose Statement: Several studies have shown that aerobic exercise can have a positive impact on alleviating symptoms experienced by individuals with Parkinson's disease (PD). Despite this evidence, the potential benefits of exercise for both PD patients and their care partners (PD dyad) remain unexplored. This research project investigates the effectiveness, therapeutic collaborations, and physical outcomes of a virtual reality (VR) tandem cycling program specifically designed for PD dyads.

Methods: Following approval from the Prisma Health Institutional Review Board, individuals with PD were identified and screened by clinical neurologists. The pre-testing measures for PD dyads (N=9) included emotional and cognitive status …

Using Artificial (Ai) To Predict A Structure Of Protein Complex, Yiqing Zang

SACAD: John Heinrichs Scholarly and Creative Activity Days

Proteins play pivotal roles in essential life processes and elucidating their three-dimensional (3D) structures is crucial for understanding their functions. AlphaFold2, an advanced artificial intelligence-based method developed by Google DeepMind, has emerged as a promising tool for predicting protein structures. In this study, we evaluated the predictive capabilities of AlphaFold2. Our findings highlight AlphaFold2's efficacy in providing valuable insights into protein structure prediction, albeit with certain limitations. While AlphaFold2 represents a significant advancement in the field, its utility is best realized when integrated with complementary experimental approaches. Consequently, combining the strengths of AlphaFold2 with experimental validation remains essential for achieving …