Biochemistry, Biophysics, and Structural Biology Commons^™

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 …

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 …

Trip13’S Crucial Role In Pancreatic Cancer Progression, Swati Dhasmana, Anupam Dhasmana, Stella Rios, Iris A. Enriquez-Perez, Sheema Khan, Farrukh Afaq, Upender Manne, Murali M. Yallapu, Subhash Chauhan

Research Symposium

Background: Pancreatic cancer, characterized by its high mortality rate, stands as one of the most aggressive cancer forms. The projected surge in pancreatic cancer-related deaths, making it the second leading cause in the United States by 2030, underscores the urgency for effective early screening tools. This study employs data mining methods to scrutinize bioinformatic data surrounding TRIP13. Examining differential expression across various cancers, correlating TRIP13 expression with pancreatic cancer stages, exploring associations with common cancer genes, and analyzing overall survival rates constitute the core investigations. Integrated with molecular biology techniques, the study further quantifies TRIP13 expression in progressive pancreatic cancer …

Investigating Optimal Laboratory Growth Conditions Of Gracilibacillus Halotolerans In Media Supplemented With Salt, Isaac Young

Annual Research Symposium

As interest continues to grow in the field of persister cells and their morphology, there arises an ever-evolving desire to further understand specific strains of bacteria that exemplify the qualities of seemingly anomalous survival regardless of anti-bacterial treatment. In the case of the Gracilibacillus halotolerans, a halotolerant extremophile extracted from the Great Salt Lake with known persistent characteristics, uncovering its optimal growth conditions was essential for future investigations. Identifying the optimal salinity for the growth of G. halotolerans will allow us to standardize our growth methods, uncover several mechanisms of saline tolerance, and add to future investigations of persistence with …

College Of Natural Sciences 2023 Year-End Publication, College Of Natural Sciences

College of Natural Sciences Newsletters and Reports

Page 1 Dean's Message
Page 3 Department Highlights
Page 4 One Day for State
Page 5 Noble Prize Winner Speaks on Campus
Page 6-7 Faculty Excellence
Page 8-9 Student Excellence
Page 10 Outreach Program
Page 10 Events and Traditions
Page 11 Connections Abroad
Page 12 Student Spotlight
Page 13 Alumni Spotlight
Page 14 First Ever Drone Day
Page 15 Grand Opening of POET Bioproducts Center
Page 16 Work Anniversaries

Ksp1 Is An Autophagic Receptor Protein For The Snx4-Assisted Autophagy Of Ssn2/Med13, Sara E Hanley, Stephen D Willis, Steven J Doyle, Randy Strich, Katrina F Cooper

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Ksp1 is a casein II-like kinase whose activity prevents aberrant macroautophagy/autophagy induction in nutrient-rich conditions in yeast. Here, we describe a kinase-independent role of Ksp1 as a novel autophagic receptor protein for Ssn2/Med13, a known cargo of Snx4-assisted autophagy of transcription factors. In this pathway, a subset of conserved transcriptional regulators, Ssn2/Med13, Rim15, and Msn2, are selectively targeted for vacuolar proteolysis following nitrogen starvation, assisted by the sorting nexin heterodimer Snx4-Atg20. Here we show that phagophores also engulf Ksp1 alongside its cargo for vacuolar proteolysis. Ksp1 directly associates with Atg8 following nitrogen starvation at the interface of an Atg8-family interacting …

Protein-Protein Interactions In Cell Cycle Proteins: An In Silico Investigation Of Two Important Players, Andriele Eichner

Dissertations, Theses, and Capstone Projects

The examination of the cell cycle carries significant implications for the biology, health, and overall existence of all living things. These implications span from the development and growth of these organisms to the aging process and cancer, as well as the potential of stem cell therapies to repair diseases and injuries. Numerous proteins of the cell cycle are essential for cellular division and proliferation and are widely conserved over the course of evolution. In this work, we aimed to investigate the molecular processes of protein-protein interactions in cell cycle proteins, centering on two key players: Cdc6 in budding yeast and …

Tail-Tape-Fused Virion And Non-Virion Rna Polymerases Of A Thermophilic Virus With An Extremely Long Tail, Anastasiia Chaban, Leonid Minakhin, Ekaterina Goldobina, Brain Bae, Yue Hao, Sergei Borukhov, Leena Putzeys, Maarten Boon, Florian Kabinger, Rob Lavigne, Kira S Makarova, Eugene V Koonin, Satish K Nair, Shunsuke Tagami, Konstantin Severinov, Maria L Sokolova

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Thermus thermophilus bacteriophage P23-45 encodes a giant 5,002-residue tail tape measure protein (TMP) that defines the length of its extraordinarily long tail. Here, we show that the N-terminal portion of P23-45 TMP is an unusual RNA polymerase (RNAP) homologous to cellular RNAPs. The TMP-fused virion RNAP transcribes pre-early phage genes, including a gene that encodes another, non-virion RNAP, that transcribes early and some middle phage genes. We report the crystal structures of both P23-45 RNAPs. The non-virion RNAP has a crab-claw-like architecture. By contrast, the virion RNAP adopts a unique flat structure without a clamp. Structure and sequence comparisons of …

Why Should Early-Career Scientists Publish In Society Journals, Stephen K. Dolan, Lori D. Banks, Wenqi Yu

Molecular Biosciences Faculty Publications

In this editorial, written by early-career scientists, we advocate for the invaluable role of society journals in our scientific community. By choosing to support these journals as authors, peer reviewers, and as editors, we can reinforce our academic growth and benefit from their re-investment back into the scientific ecosystem. Considering the numerous clear merits of this system for future generations of microbiologists and more broadly, society, we argue that early-career researchers should publish our high-quality research in society journals to shape the future of science and scientific publishing landscape.

The Inaugural Mbio Junior Editorial Board—Lessons Learned And The Path Forward Toward Improving The Peer Review Process, Cynthia Ayefoumi Adinortey, Stephen K. Dolan, Sarah Doore, Rebeccah Lijek, Diana Priscila Pires, Wenqi Yu, Elizabeth B. Draganova, Lennart Schada Von Borzyskowski

Molecular Biosciences Faculty Publications

The inaugural Junior Editorial Board (JEB) of mBio consisted of 64 early-career researchers active from 2022 to 2023. The goal of the JEB was to train early-career researchers in the art of peer review under the guidance of experienced editors. JEB members gained hands-on experience in peer review by participating in modules detailing the publishing process through the lenses of the journal, editor, and reviewer. Ultimately, JEB members applied this new knowledge by reviewing mBio manuscripts. Here, we summarize the background, the mission, and the achievements of the first mBio JEB. We also include possible trajectories for the future editions …

Fused In Sarcoma Regulates Glutamate Signaling And Oxidative Stress Response, Chiong-Hee Wong, Abu Rahat, Howard C Chang

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Mutations in fused in sarcoma (fust-1) are linked to ALS. However, how these ALS causative mutations alter physiological processes and lead to the onset of ALS remains largely unknown. By obtaining humanized fust-1 ALS mutations via CRISPR-CAS9, we generated a C. elegans ALS model. Homozygous fust-1 ALS mutant and fust-1 deletion animals are viable in C. elegans. This allows us to better characterize the molecular mechanisms of fust-1-dependent responses. We found FUST-1 plays a role in regulating superoxide dismutase, glutamate signaling, and oxidative stress. FUST-1 suppresses SOD-1 and VGLUT/EAT-4 in the nervous system. FUST-1 also regulates synaptic AMPA-type glutamate receptor …

Can Biology Define A Human Life?, Katelyn De Leon

Regis University Student Publications (comprehensive collection)

I grew up contemplating the concept of life. From my Catholic grandmother to my pediatrician mother, I always received mixed perspectives on the hot topics of abortions, vaccines, and embryo use. I found that the controversy lies in an ambiguous, mixed understanding of what constitutes a human life. From biochemical approaches to extraterrestrial life forms and spirituality there is no clear, coherent all-encompassing definition of life. However, that does not mean we can merely agree to disagree. The concept of a human life has drastic implications on our everyday lives. An insufficient definition has, and will continue to, diminish quality …

Assessing Lipid Composition Of Cell Membrane In Escherichia Coli Under Aerobic And Anaerobic Conditions, Isabelle Johnson

Undergraduate Theses, Professional Papers, and Capstone Artifacts

Escherichia coli is a highly studied model organism that is tightly tied to the mammalian gastrointestinal system. This microorganism has the capability to be a beneficial gut microbe or a life-threatening pathogen. In this study, the lipid membrane of Escherichia coli was investigated using Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) to observe the change in its composition in aerobic and anaerobic conditions. Evidence of desaturation was discovered in the spectra, though more investigation is needed to understand the metabolic processes and drives that result in this change. Elucidation of these pathways in the future could result in …

Deep Learning Image Analysis To Isolate And Characterize Different Stages Of S-Phase In Human Cells, Kevin A. Boyd, Rudranil Mitra, John Santerre, Christopher L. Sansam

SMU Data Science Review

Abstract. This research used deep learning for image analysis by isolating and characterizing distinct DNA replication patterns in human cells. By leveraging high-resolution microscopy images of multiple cells stained with 5-Ethynyl-2′-deoxyuridine (EdU), a replication marker, this analysis utilized Convolutional Neural Networks (CNNs) to perform image segmentation and to provide robust and reliable classification results. First multiple cells in a field of focus were identified using a pretrained CNN called Cellpose. After identifying the location of each cell in the image a python script was created to crop out each cell into individual .tif files. After careful annotation, a CNN was …

Repositioning Propranolol To Block Mitogenic Signaling In Breast Cancer, Alexa Noel Montoya

Open Access Theses & Dissertations

Breast cancer is the second most diagnosed cancer among women and is about 30% of all new cases of female cancers each year. It is projected that 1 in 8 every U.S. woman (about 13%) develop invasive breast cancer over the course of her lifetime. While advances in cancer research have made it possible to elucidate several breast cancer genomic subtypes, and develop new novel therapies, many of these agents are associated with significant toxicity, as well as high costs. A retrospective cross-sectional study of 404 breast cancer patients was performed to determine the effect of β-blocker usage on tumor …

Characterization Of The Effects Of The Pyrazolopyrimidine Inhibitor Grassofermata (Nav-2729) In The Eukaryotic Pathogen Trypanosoma Brucei, Kristina Marie Parman

All Dissertations

The protozoan pathogen, Trypanosoma brucei, is the causative agent of sleeping sickness in humans and nagana in livestock in sub-Saharan Africa. T. brucei cycles between tsetse fly and mammalian hosts, and it is adapted to survive in diverse host tissues. Variant Surface Glycoprotein (VSG) plays a key role in immune evasion in the mammalian host. The VSG membrane anchor requires two myristates, 14-carbon saturated fatty acids (FAs) that are scarce in the host. T. brucei can synthesize FAs de novo, but also readily takes up exogenous FAs, despite lacking homologs to fatty acid uptake proteins found in other …

Amyloid Fibrils Of Human Fgf-1 Induced By Different Detergents, Zeina Ismael Ibrahem Alraawi

Graduate Theses and Dissertations

Nature achieves molecular self-assembly through the ordered growth of nanoscale building blocks with high efficiency to fabricate macromolecular architectures. One example of self- assembly is peptides folding onto protein is one of the most astounding biological self-assembly processes. When proteins aggregate to form amyloid fibers, the secondary structure of the protein converts from its native state to a cross-beta-sheet. Fibroblast growth factors (FGFs) possess an essential role in neuronal survival during development. In addition, they are involved in neural stem cell (NSC) proliferation. Fibroblast growth factors (FGFs) are well known to be synthesized in the central nervous system (CNS) and …

Characterization Of Human Fibroblast Growth Factor 2 Variant To Determine Effects On Structure, Stability, And Cell Proliferation, Ryan Layes

Graduate Theses and Dissertations

Fibroblast growth factors (FGFs) are a family of cell signaling proteins conserved across multiple species. Each individual FGF elicits different cellular functions including, but not limited to, proliferation, migration, differentiation, angiogenesis, and wound healing. One of the most studied members, fibroblast growth factor 2 (FGF2), has demonstrated substantial wound healing capacity in a wide range of tissues including skeletal, muscular, neural, respiratory, epithelial, and cardiovascular. This ability makes FGF2 a potential therapeutic for a wide range of conditions and injuries. However, due to a short half-life at room temperature, therapeutic use of FGF2 is limited. It has been demonstrated that …

Protein Trafficking In The Endoplasmic Reticulum Mediated By A Tpr-Containing Adapter Protein, Nathan P. Canniff

Doctoral Dissertations

The endoplasmic reticulum (ER) is a large, multifunctional organelle that acts as the entrance into the secretory pathway, which accounts for the folding and maturation of approximately one third of the human proteome. It is the largest organelle in most cell types and is comprised of a single lumen and a contiguous membrane. The ER is responsible for a multitude of roles including protein translocation, folding, maturation, quality control, and glycosylation to name a few. These processes are buoyed by a large collection of chaperones and cochaperones, the largest subfamily of which is characterized by the presence of tetratricopeptide repeat …

Caulobacter Clpxp Adaptor Popa’S Domain Interactions In The Adaptor Hierarchy Of Ctra Degradation, Thomas P. Scudder

Masters Theses

The degradation and recycling of protein is a process essential for the maintenance and regulation of cellular function. More specifically, in Caulobacter crescentus, the ClpXP protease is responsible for driving progression through the cell cycle and protein quality control. This protease utilizes three known adaptors to selectively degrade proteins that initiate different stages of development. This thesis will elaborate on the specific binding interface on one of these adaptors, PopA, with another, RcdA, and focus in on specific residues on PopA and investigate their roles in adaptor binding and delivery of CtrA, the master regulator of Caulobacter. Finally, I …

Using Hyperosmotic Shock To Study The Cell Wall Of Myxococcus Xanthus, Ian Sabol

Harrisburg University Research Symposium: Highlighting Research, Innovation, & Creativity

No abstract provided.

Effects Of Growth Rate On Peptidoglycan Crosslink Density Of E. Coli Using Fluorescent Labeling, Morgan Olszewski

Harrisburg University Research Symposium: Highlighting Research, Innovation, & Creativity

Peptidoglycan (PG) is a polymer composed of polysaccharides and crosslinked peptide chains found in bacterial cell walls. It helps to protect the cell from environmental stress and maintain cell morphology throughout its life cycle and further generations. The PG is made up of two sugars, N-acetyl muramic acid (NAM) and N-acetyl glucosamine (NAG). NAM and NAG are connected by glycosidic linkages to form repeated chains. The chains are formed in layers, which are interconnected via a polypeptide stem linked by a peptide bridge. During cell growth, continuous turnover of existing PG occurs by severing existing crosslinks, inserting new PG into …

Molecular Event In Hrp Apoptosis, Laura Valdez

Research Colloquium

Background: Human retinal pericytes (HRP) are contractile cells providing support for endothelial cells of capillaries, essential in the regulation of retinal vasculature. Early stages of DR are characterized by the loss of HRP, leading to angiogenesis. Our preliminary studies identified monocyte-derived macrophages secrete TGF-β1, inducing the expression and secretion of a TGFβ1-Induced, pro-apoptotic BIGH3 protein leading to apoptosis of HRP. Based on a preliminary study in renal cells (unpublished data), CTP with an RGD domain is released from BIGH3 by proteolysis leading to renal cell apoptosis. In the present study, we employed Western Blots to determine if a similar molecular …

Irbp In Diabetic Retinopathy – Cell Culture & Ophthalmic Pathology Studies, Laura Valdez

Research Colloquium

Background: Interphotoreceptor-Retinoid-Binding-Protein (IRBP) is restricted to the subretinal space by the external limiting membrane and RPE zonulae occludens. Its expression is reduced in diabetic retinopathy (DR) and increased expression is protective. Hypoxia decreases viable conelike photoreceptors (661W) but increased VEGF, suggesting a role of photoreceptors in proliferative DR (PDR) (Rodriguez et al, Arch Clin Exp. Ophthal 3:23,2021). Here, we investigated the effects of high glucose and VEGF on IRBP expression by 661W and rod-like Y79 cells and distribution of IRBP and albumin in human globes with PDR and NPDR.

Methods:  661W and Y79 cells were cultured in DMEM or RPMI …

College Of Natural Sciences Newsletter, September - October 2023, College Of Natural Sciences

College of Natural Sciences Newsletters and Reports

Page 1 Dean's Message
Page 2 New Faculty an Staff for the Fall 2023 Semester
Page 3 Awards
Page 4 Student Ambassadors in CNS
Page 5 Meet our Jacks
Page 6-8 Events
Page 9-11 Media Coverage of CNS
Page 12-13 Spring 2023 Dean's List
Page 14 Open PRAIRIE Data

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 …

Natural Remedies To Combat Aberrant Hallmark Signatures Including Altered Glycosylation In Oral Carcinoma, Kruti A. Mehta, Jayendra B. Patel, Prabhudas S. Patel

Research Symposium

Background: Tobacco associated oral cancers remain a major concern in India with higher incidence and mortality making it an Indian-centric burning issue. To combat this dreadful disease, we investigated effects of certain natural compounds on the hallmark signatures including glycosylation transcripts levels in oral carcinoma.

Methods: The tongue carcinoma cells- SAS cells were treated with tobacco compounds, natural compounds and Cisplatin. RNA was isolated from the cells and converted to cDNA. RT-qPCR was performed to evaluate expression levels of various genes.

Results: The treatment of tobacco compounds resulted in similar pattern of altered makers (ST3GAL1, NEU3, FUT5, FUT6, MMP2, BCL2) …

Hpv Imprints In Western India: The Overlooked Criteria For Cancer Profiling, Ashi R. Thobias, Jayendra B. Patel, Prabhudas P. Patel

Research Symposium

Background: In India, HPV infection detection for cancer-typing has been largely evaded. Especially, data on prevalence of HPV types other than the highly prevalent HPV 16 and 18 are lacking, particularly from the western region. Thus, present study aimed to evaluate prevalence of HPV strains in three most prevailing cancers in India i.e. cervical, oral and oropharyngeal cancer.

Materials & methods: DNA was isolated from tissue samples of 400 cervical cancer cases, 127 oral cancer cases and 75 oropharyngeal cancer cases and endpoint PCR was performed using degenerative primers MY 09/11, GP 5+/6+ and CP I/II. TS-PCR was conducted to …

Identification Of Tectorigenin As A Natural Pro-Hypoxia Compound: Implications In Modulation Of Cellular Differentiation And Senescence, Mallika Khurana, Renu Wadhwa, Sunil Kaul

Research Symposium

Background: Hypoxia, a suboptimal level of oxygen, evokes stress response in cells and activated hypoxia signaling has been largely established as a pro-metastasis and pro-angiogenic factor for tumor cells. On the other hand, age-related neurodegenerative disorders are characterized by hypoxic environment, accumulation of molecular garbage and induction of premature senescence. Several recent studies have reported anti-stress impact of the intermittent induction of hypoxia signaling in these cells.

Methods: Screening of a phytochemical library using Hypoxia Responsive Element (HRE) driven luciferase as a reporter was carried out to identify hypoxia-modulating phytochemicals. Activation of HIF-1a (master regulator of hypoxia signaling) was validated …