Ateneo de Manila University
Murray State University
University of Massachusetts Amherst
National Organization for Drug Control and Research (NODCAR), Giza, Cairo.
University of Wisconsin Milwaukee
Louisiana State University and Agricultural and Mechanical College
University of Arkansas, Fayetteville
Old Dominion University
Technological University Dublin
Purification Of Recombinant E. Coli Topoisomerase Iii For Structure-Based Drug Design Using Protein Crystallization,
2024
Florida International University
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,
2024
Florida International University
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 …
The Role Of Med13 In Proteaphagy,
2024
Rowan University
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,
2024
University of Nebraska at Omaha
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 …
Understanding Taf13 (Tata Box-Binding Protein-Associated Factor 13) Upregulation In Eukaryotic Cells,
2024
University of Tennessee at Chattanooga
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 …
A Review Of Rheb Activation Of Mtorc1 And The Great Mystery Of One Missing Gef,
2024
Liberty University
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 …
Molecular Characterization Of Stress Response In Western Honey Bee (Apis Mellifera),
2024
The University of Southern Mississippi
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 …
Trna Anticodon Cleavage By Target-Activated Crispr-Cas13a Effector,
2024
Rutgers University - New Brunswick/Piscataway
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 …
Predictive And Prognostic Biomarkers And Tumor Antigens For Targeted Therapy In Urothelial Carcinoma,
2024
Thomas Jefferson University
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 …
Upregulation Of The Predominant Cystic Fibrosis Causing Mutation Df508-Cftr By Triazole Compounds In Epithelial Cells,
2024
Mississippi University for Women
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 …
Discovery Of A Small-Molecule Inhibitor That Traps Polθ On Dna And Synergizes With Parp Inhibitors,
2024
Thomas Jefferson University
Discovery Of A Small-Molecule Inhibitor That Traps Polθ On Dna And Synergizes With Parp Inhibitors, William Fried, Mrityunjay Tyagi, Leonid Minakhin, Gurushankar Chandramouly, Taylor Tredinnick, Mercy Ramanjulu, William Auerbacher, Marissa L Calbert, Timur Rusanov, Trung Hoang, Nikita Borisonnik, Robert Betsch, John Krais, Yifan Wang, Umeshkumar Vekariya, John Gordon, George Morton, Tatiana Kent, Tomasz Skorski, Neil Johnson, Wayne Childers, Xiaojiang Chen, Richard Pomerantz
Department of Biochemistry and Molecular Biology Faculty Papers
The DNA damage response (DDR) protein DNA Polymerase θ (Polθ) is synthetic lethal with homologous recombination (HR) factors and is therefore a promising drug target in BRCA1/2 mutant cancers. We discover an allosteric Polθ inhibitor (Polθi) class with 4-6 nM IC50 that selectively kills HR-deficient cells and acts synergistically with PARP inhibitors (PARPi) in multiple genetic backgrounds. X-ray crystallography and biochemistry reveal that Polθi selectively inhibits Polθ polymerase (Polθ-pol) in the closed conformation on B-form DNA/DNA via an induced fit mechanism. In contrast, Polθi fails to inhibit Polθ-pol catalytic activity on A-form DNA/RNA in which the enzyme binds in …
Social Media Does Not Elicit A Physiological Stress Response As Measured By Heart Rate And Salivary Cortisol Over 20-Minute Sessions Of Cell Phone Use,
2024
College of Western Idaho
Social Media Does Not Elicit A Physiological Stress Response As Measured By Heart Rate And Salivary Cortisol Over 20-Minute Sessions Of Cell Phone Use, Suzanne Oppenheimer, Laura Bond, Charity Smith
Biomolecular Research Center Publications and Presentations
The pervasive use of social media has raised concerns about its potential detrimental effects on physical and mental health. Others have demonstrated a relationship between social media use and anxiety, depression, and psychosocial stress. In light of these studies, we examined physiological indicators of stress (heart rate to measure autonomic nervous system activation and cortisol to assess activity of the hypothalamic-pituitary-adrenal axis) associated with social media use and investigated possible moderating influences of sex, age, and psychological parameters. We collected physiological data from 59 subjects ranging in age from 13 to 55 across two cell phone treatments: social media use …
The Impact Of Mutations In The Arabidopsis Apetela (Ap3) Gene,
2024
Fort Hays State University
The Impact Of Mutations In The Arabidopsis Apetela (Ap3) Gene, Hazel R. Frans, Tara Phelps-Durr
SACAD: John Heinrichs Scholarly and Creative Activity Days
The purpose of this research is to understand the molecular functioning of the Arabidopsis thaliana Apetela (Ap3) gene. We created mutations in two sites of the gene, AP3-3 and AP3-5. These are predicted to change AP3 protein structure, which may result in a mutated flower. Analyzing the effects of new mutations allows an understanding of protein formation both in plants and humans.
Parp2 Promotes Break Induced Replication-Mediated Telomere Fragility In Response To Replication Stress,
2024
Thomas Jefferson University
Parp2 Promotes Break Induced Replication-Mediated Telomere Fragility In Response To Replication Stress, Daniela Muoio, Natalie Laspata, Rachel L Dannenberg, Caroline Curry, Simone Darkoa-Larbi, Mark Hedglin, Shikhar Uttam, Elise Fouquerel
Department of Biochemistry and Molecular Biology Faculty Papers
PARP2 is a DNA-dependent ADP-ribosyl transferase (ARTs) enzyme with Poly(ADP-ribosyl)ation activity that is triggered by DNA breaks. It plays a role in the Base Excision Repair pathway, where it has overlapping functions with PARP1. However, additional roles for PARP2 have emerged in the response of cells to replication stress. In this study, we demonstrate that PARP2 promotes replication stress-induced telomere fragility and prevents telomere loss following chronic induction of oxidative DNA lesions and BLM helicase depletion. Telomere fragility results from the activity of the break-induced replication pathway (BIR). During this process, PARP2 promotes DNA end resection, strand invasion and BIR-dependent …
In Silico Identification Of Small Molecule Agonist Binding Sites On Kcc2,
2024
Noorda College of Osteopathic Medicine
In Silico Identification Of Small Molecule Agonist Binding Sites On Kcc2, Kenyon Mitchell, Alfred Amendolara, Ruth Hunter, Jaden Miner, Andrew Payne
Annual Research Symposium
Purpose: Potassium-Chloride Cotransporter 2 (KCC2) is a neuronal membrane protein specific to the central nervous system. It is responsible for removing Cl- ions from the intracellular space, maintaining a normal Cl- gradient essential for proper function at inhibitory synapses. Dysregulation causes an upward shift in the Cl- reversal potential resulting in a hyperexcitable state of the postsynaptic neuron. Existing literature indicates that KCC2 may be involved in the addiction pathway of a variety of drugs of abuse, including opioids and alcohol. This makes KCC2 an attractive potential drug target when treating substance use disorders. A novel direct KCC2 agonist, VU0500469, …
Tools For Biomolecular Modeling And Simulation,
2024
Southern Methodist University
Tools For Biomolecular Modeling And Simulation, Xin Yang
Mathematics Theses and Dissertations
Electrostatic interactions play a pivotal role in understanding biomolecular systems, influencing their structural stability and functional dynamics. The Poisson-Boltzmann (PB) equation, a prevalent implicit solvent model that treats the solvent as a continuum while describes the mobile ions using the Boltzmann distribution, has become a standard tool for detailed investigations into biomolecular electrostatics. There are two primary methodologies: grid-based finite difference or finite element methods and body-fitted boundary element methods. This dissertation focuses on developing fast and accurate PB solvers, leveraging both methodologies, to meet diverse scientific needs and overcome various obstacles in the field.
A Comparison Of In Vitro Studies Between Cobalt(Iii) And Copper(Ii) Complexes With Thiosemicarbazone Ligands To Treat Triple Negative Breast Cancer,
2024
Old Dominion University
A Comparison Of In Vitro Studies Between Cobalt(Iii) And Copper(Ii) Complexes With Thiosemicarbazone Ligands To Treat Triple Negative Breast Cancer, Duaa R. Alajroush, Chloe B. Smith, Brittney F. Anderson, Ifeoluwa T. Oyeyemi, Stephen J. Beebe, Alvin A. Holder
Undergraduate Research Symposium
Triple negative breast cancer (TNBC) is one of the most aggressive forms of breast cancer, and disproportionately affects African American women. TNBC cells lack the common hormone receptors that many pre-existing cancer treatments target. Fortunately, metal-based complexes with thiosemicarbazone ligands have gained significant attention for their potential as anti-cancer agents. Cobalt(III) complex ([Co(phen)2(MeATSC)](NO3)3•1.5H2O•C2H5OH]) and Copper(II) complex ([Cu(acetylethTSC)Cl]Cl•0.25C2H5OH) specifically have properties of high toxicity, which can contribute to decreased cancer cell activity. The effects of these complexes are currently being investigated on cancerous and non-cancerous breast cell lines. The cytotoxic effect of the cobalt(lll) complex and the copper(ll) complex was analyzed …
Blocking The Dimerization Of Polyglutamine-Expanded Androgen Receptor Protects Cells From Dht-Induced Toxicity By Increasing Ar Turnover,
2024
Thomas Jefferson University
Blocking The Dimerization Of Polyglutamine-Expanded Androgen Receptor Protects Cells From Dht-Induced Toxicity By Increasing Ar Turnover, Allison Lisberg, Yuhong Liu, Diane E. Merry
Department of Biochemistry and Molecular Biology Faculty Papers
Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular degenerative disease caused by a polyglutamine expansion in the androgen receptor (AR). This mutation causes AR to misfold and aggregate, contributing to toxicity in and degeneration of motor neurons and skeletal muscle. There is currently no effective treatment or cure for this disease. The role of an interdomain interaction between the amino- and carboxyl-termini of AR, termed the N/C interaction, has been previously identified as a component of androgen receptor-induced toxicity in cell and mouse models of SBMA. However, the mechanism by which this interaction contributes to disease pathology is unclear. …
Biomarkers For Managing Neurodegenerative Diseases,
2024
Thomas Jefferson University
Biomarkers For Managing Neurodegenerative Diseases, Lara Cheslow, Adam E. Snook, Scott A. Waldman
Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers
Neurological disorders are the leading cause of cognitive and physical disability worldwide, affecting 15% of the global population. Due to the demographics of aging, the prevalence of neurological disorders, including neurodegenerative diseases, will double over the next two decades. Unfortunately, while available therapies provide symptomatic relief for cognitive and motor impairment, there is an urgent unmet need to develop disease-modifying therapies that slow the rate of pathological progression. In that context, biomarkers could identify at-risk and prodromal patients, monitor disease progression, track responses to therapy, and parse the causality of molecular events to identify novel targets for further clinical investigation. …
In Silico Analysis Of C-Type Lectins As Co-Infection Receptors Of Dengue And Chikungunya Viruses In Aedes Aegypti,
2024
Biology Program, Faculty of Tarbiyah and Education, Islamic State University of Mataram, Mataram 83125, Indonesia
In Silico Analysis Of C-Type Lectins As Co-Infection Receptors Of Dengue And Chikungunya Viruses In Aedes Aegypti, Munawir Sazali, R. C. Hidayat Soesilohadi, Nastiti Wijayanti, Tri Wibawa, Arif Nur Muhammad Ansori
Makara Journal of Science
Aedes aegypti is a primer vector of dengue virus (DENV) and chikungunya virus (CHIKV). The susceptibility of mosquitoes to DENV and CHIKV depends on their recognition receptor of pathogens. C-type lectins (CTLs) are an important mediator of virus infection in A. aegypti. This study aims to identify potential receptors and determine the binding affinity between ligand–receptor interaction, CTLs and virus envelopes (DENV-1, 2, 3, and 4 and CHIKV) interaction based on in silico analysis. Sample sequences were obtained from GenBank (NCBI), and 10 CTLs were acquired from VectorBase. Homology modeling based on a minimum standard of 20% was processed …
