Biochemistry, Biophysics, and Structural Biology Commons^™

Isothiocyanates Potentiate Tazemetostat-Induced Apoptosis By Modulating The Expression Of Apoptotic Genes, Members Of Polycomb Repressive Complex 2, And Levels Of Tri-Methylating Lysine 27 At Histone 3 In Human Malignant Melanoma Cells, Ioannis Anestopoulos, Ioannis Paraskevaidis, Sotiris Kyriakou, Lambrini E. Giova, Dimitrios T. Trafalis, Sotiris Botaitis, Rodrigo Franco, Aglaia Pappa, Mihalis L. Panayiotidis

School of Veterinary and Biomedical Sciences: Faculty Publications

In this study, we utilized an in vitro model consisting of human malignant melanoma as well as non-tumorigenic immortalized keratinocyte cells with the aim of characterizing the therapeutic effectiveness of the clinical epigenetic drug Tazemetostat alone or in combination with various isothiocyanates. In doing so, we assessed markers of cell viability, apoptotic induction, and expression levels of key proteins capable of mediating the therapeutic response. Our data indicated, for the first time, that Tazemetostat caused a significant decrease in viability levels of malignant melanoma cells in a dose- and time-dependent manner via the induction of apoptosis, while non-malignant keratinocytes were …

Revascularization Strategies For Acute And Chronic Mesenteric Ischemia: A Narrative Review, Jacob J Gries, Takashi Sakamoto, Bing Chen, Hafeez Ul Hassan Virk, Mahboob Alam, Chayakrit Krittanawong

Faculty, Staff and Students Publications

Mesenteric ischemia is a challenging condition characterized by insufficient blood perfusion to the mesentery and, consequently, intestinal tissues that continues to perplex clinicians. Despite its low prevalence, the condition’s variable clinical presentation and elusive radiographic diagnosis can delay life-saving interventions in the acute setting and deteriorate the quality of life of patients when left undiagnosed or misdiagnosed. Purpose: Review and summarize recent diagnostic updates and emergent intervention strategies for acute and chronic mesenteric ischemia. Methods: A narrative review of all relevant studies from January 2022 through September 2023. Results: A total of 11 studies from MEDLINE, supplemented with 44 studies …

Editorial: Pharmacology Of Endocrine Related Gpcrs, Francesco De Pascali, Aylin Hanyaloglu, Frederic Jean-Alphonse, Francesco Potì, Eric Reiter

Department of Biochemistry and Molecular Biology Faculty Papers

No abstract provided.

Long Non-Coding Rna As A Potential Diagnostic Tool In Coronary Artery Diseases - A Systematic Review, Arthi Sri A.S, Vishnu Priya Veeraraghavan

Annual Research Symposium

POSTER - SYSTEMATIC REVIEW - LONG NON CODING RNAS AS DIAGNOSTIC MARKER FOR CAD

Correlation Between Salivary Levels And Tissue Expression Status Of Her2 In Breast Cancer Patients - A Cross-Sectional Study, Arthi Sri A.S, Massillamani F, Vinothkumar Thilla Sekar

Annual Research Symposium

The study aims to investigate if soluble salivary human epidermal growth factor receptor-2 (HER2) would play a role in the diagnosis of breast cancer patients and also to find out the influence of demographic and hormonal factors on the salivary HER2 levels in breast 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 …

In Vivo Dynamic Volumetric Imaging Of Mouse Testis And Epididymis With Optical Coherence Tomography†, Kohei Umezu, Guzel R Musina, Irina V Larina

Faculty, Staff and Students Publications

The implementation of live imaging in reproductive research is crucial for studying the physiological dynamics. Sperm transport is a highly dynamic process regulated by tubular contractions and luminal flows within the male reproductive tract. However, due to the lack of imaging techniques to capture these dynamics in vivo, there is little information on the physiological and biomechanical regulation of sperm transport through the male reproductive tract. Here, we present a functional in vivo imaging approach using optical coherence tomography, enabling live, label-free, depth-resolved, three-dimensional, high-resolution visualization of the mouse testis and epididymis. With this approach, we spatiotemporally captured tubular contractility …

Historical Analysis Of Urban Dust Generated By The Great Salt Lake Playa, Callum Flowerday, Jaron C. Hansen, Rebekah Stanley, Kaitlyn Brewster

ScholarsArchive Data

Historical PM10 filters, provided by the Utah Division of Air Quality, were analyzed for elemental composition of various metals. This was done using ICP-MS.

Also included, EPA PM10 historical data and bathymetry data provided by the Utah USGS.

An Observational Framework For Constructing Ozone Isopleths From Long-Term Monitoring Data: Demonstration In Salt Lake City, Utah, Callum Flowerday, Isaac Sudweeks, Brad Adams, Jaron C. Hansen

ScholarsArchive Data

EPA quality assured data, collected by the Utah Division of Air Quality, was used for this analysis.

Unimer Suppression Enables Supersaturated Homopolymer Swollen Micelles With Long-Term Stability After Glassy Entrapment, Eric R. Williams, Christian X. Ruff, Morgan Stefik

Faculty Publications

Micelle sizes are critical for a range of applications where the simple ability to adjust and lock in specific stable sizes has remained largely elusive. While micelle swelling agents are well-known, their dynamic re-equilibration in solution implies limited stability. Here, a non-equilibrium processing sequence is studied where supersaturated homopolymer swelling is combined with glassy-core (“persistent”) micelles. This path-dependent process was found to sensitively depend on unimer concentration as revealed by DLS, SAXS, and TEM analysis. Here, lower-selectivity solvent combinations led to the formation of unimer-homopolymer aggregates and eventual precipitation, reminiscent of anomalous micellization. In contrast, higher-selectivity solvents enabled supersaturated homopolymer …

Unimer Suppression Enables Supersaturated Homopolymer Swollen Micelles With Long-Term Stability After Glassy Entrapment, Eric R. Williams, Christian X. Ruff, Morgan Stefik

Faculty Publications

Micelle sizes are critical for a range of applications where the simple ability to adjust and lock in specific stable sizes has remained largely elusive. While micelle swelling agents are well-known, their dynamic re-equilibration in solution implies limited stability. Here, a non-equilibrium processing sequence is studied where supersaturated homopolymer swelling is combined with glassy-core (“persistent”) micelles. This path-dependent process was found to sensitively depend on unimer concentration as revealed by DLS, SAXS, and TEM analysis. Here, lower-selectivity solvent combinations led to the formation of unimer-homopolymer aggregates and eventual precipitation, reminiscent of anomalous micellization. In contrast, higher-selectivity solvents enabled supersaturated homopolymer …

Evidence That Aquaporin 11 (Aqp11) In The Spiny Dogfish (Squalus Acanthias) May Represent A Pseudogene, Christopher P. Cutler, Meghan Canicatti, Esosa Omoregie

Biology: Faculty Publications

Various attempts to amplify an AQP11 cDNA from tissues of the spiny dogfish (Squalus acanthias) were made. Two pairs of deoxy-inosine-containing degenerate primers were designed based on conserved amino acid sequences from an AQP11 alignment. These primers yielded some faint bands from gill cDNA that were sequenced. Blast searches with the sequences showed they were not AQP11. An elasmobranch AQP11 nucleotide sequence alignment was produced to identify conserved regions to make further degenerate primers. One primer pair produced a short 148 bp fragment showing particularly strong amplification in gill and intestine. It was sequenced and represented a piece of the …

Use Of Dft Calculations As A Tool For Designing New Solvatochromic Probes For Biological Applications, Cynthia M. Dupureur

Educator Preparation & Leadership Faculty Works

The intramolecular charge transfer behavior of push–pull dyes is the origin of their sensitivity to environment. Such compounds are of interest as probes for bioimaging and as biosensors to monitor cellular dynamics and molecular interactions. Those that are solvatochromic are of particular interest in studies of lipid dynamics and heterogeneity. The development of new solvatochromic probes has been driven largely by the need to tune desirable properties such as solubility, emission wavelength, or the targeting of a particular cellular structure. DFT calculations are often used to characterize these dyes. However, if a correlation between computed (dipole moment) and experimentally measured …

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 Departmental Research

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 …

An Itpa Enzyme With Improved Substrate Selectivity, Nicholas E. Burgis, Kandise Vanwormer, Devin Robbins, Jonathan Smith

Chemistry and Biochemistry Faculty Publications

Recent clinical data have identified infant patients with lethal ITPA deficiencies. ITPA is known to modulate ITP concentrations in cells and has a critical function in neural development which is not understood. Polymorphism of the ITPA gene affects outcomes for both ribavirin and thiopurine based therapies and nearly one third of the human population is thought to harbor ITPA polymorphism. In a previous site-directed mutagenesis alanine screen of the ITPA substrate selectivity pocket, we identified the ITPA mutant, E22A, as a gain-of function mutant with enhanced ITP hydrolysis activity. Here we report a rational enzyme engineering experiment to investigate the …

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

Mitochondrial Quality Control By Tail-Anchored Proteins, Jose M. Delgado

Dartmouth College Ph.D Dissertations

Autophagy is a lysosome-mediated pathway responsible for the degradation of unwanted cytosolic content. During autophagy, cytoplasmic components are enveloped by a newly generated vesicle (the autophagosome), trafficked to the lysosome, and degraded. The power of autophagy lies in its ability to selectively target specific substrates for degradation—a phenomenon known as selective autophagy.

Specialized proteins known as selective autophagy receptors play a crucial role in identifying and targeting autophagy cargo. Although historically overlooked as potential regulators, our understanding of autophagy receptors is evolving beyond the assumption that receptors merely bridge targets to pre-formed autophagosomal membranes. Previous insights were often based on …

Cold-Inducible Rna Binding Protein Impedes Breast Tumor Growth In The Pymt Murine Model For Breast Cancer, Daniel A. Lujan, Joey L. Ochoa, Ellen J. Beswick, Tamara A. Howard, Helen J. Hathaway, Nora I. Perrone-Bizzozero, Rebecca S. Hartley

Markey Cancer Center Faculty Publications

RNA binding proteins (RBPs) post-transcriptionally regulate gene expression by associating with regulatory sequences in the untranslated regions of mRNAs. Cold-inducible RBP (CIRP) is a stress-induced RBP that was recently shown to modulate inflammation in response to cellular stress, where it increases or decreases pro-tumorigenic (proinflammatory) cytokines in different contexts. CIRP expression is altered in several cancers, including breast cancer, but the effects of CIRP on inflammation in breast cancer is not known. Here, we investigate if CIRP alters growth and the inflammatory profile of breast tumors. Transgenic mice overexpressing CIRP in the mammary epithelium were crossed with the PyMT mouse …

Anticoagulation With Osocimab In Patients With Kidney Failure Undergoing Hemodialysis: A Randomized Phase 2 Trial, Jeffrey I Weitz, László B Tankó, Jürgen Floege, Keith A A Fox, Deepak L Bhatt, Ravi Thadhani, James Hung, Ákos F Pap, Dagmar Kubitza, Wolfgang C Winkelmayer

Faculty, Staff and Students Publications

Individuals with kidney failure undergoing hemodialysis are at elevated risk for thromboembolic events. Factor (F) XI, which is in the intrinsic pathway of coagulation, is emerging as an attractive target for new anticoagulants that may be safer than existing agents. Osocimab-an inhibitory FXIa antibody-is a potential treatment option for such patients. We conducted a phase 2b, double-blind, placebo-controlled trial, in which 704 participants (448 male, 256 female) with kidney failure undergoing hemodialysis were randomized to receive lower- or higher-dose osocimab or placebo. In total, 686 participants (436 male, 250 female) received treatment for ≤18 months (planned minimal treatment period of …

Left Main Coronary Artery Disease: A Contemporary Review Of Diagnosis And Management, Muzamil Khawaja, Michael Britt, Muhammad Asad Khan, Uzair Munaf, Hassaan Arshad, Rehma Siddiqui, Hafeez Ul Hassan Virk, Mahboob Alam, Chayakrit Krittanawong

Faculty, Staff and Students Publications

Significant left main coronary artery disease is a very high-risk subgroup of coronary artery disease that is a crucial indicator of heightened morbidity and mortality rates. Despite its clinical significance, uncertainties persist regarding the optimal management strategy for patients, particularly given its phenotypic variations. Existing evidence-based guidelines offer insights into revascularization options, yet questions remain regarding long-term prognoses and clinical outcomes when comparing percutaneous coronary intervention to coronary artery bypass grafting. This comprehensive review aims to provide an in-depth analysis of contemporary strategies for the diagnosis, assessment, and treatment of left main coronary artery disease. By synthesizing current literature and …

Endothelial Cells Adopt A Pro-Reparative Immune Responsive Signature During Cardiac Injury, Hali Long, Jeffrey D Steimle, Francisco Jose Grisanti Canozo, Jong Hwan Kim, Xiao Li, Yuka Morikawa, Minjun Park, Diwakar Turaga, Iki Adachi, Joshua D Wythe, Md Abul Hassan Samee, James F Martin

Faculty, Staff and Students Publications

Modulation of the heart’s immune microenvironment is crucial for recovery after ischemic events such as myocardial infarction (MI). Endothelial cells (ECs) can have immune regulatory functions; however, interactions between ECs and the immune environment in the heart after MI remain poorly understood. We identified an EC-specific IFN responsive and immune regulatory gene signature in adult and pediatric heart failure (HF) tissues. Single-cell transcriptomic analysis of murine hearts subjected to MI uncovered an EC population (IFN-ECs) with immunologic gene signatures similar to those in human HF. IFN-ECs were enriched in regenerative-stage mouse hearts and expressed genes encoding immune responsive transcription factors …

Comparative Analysis Of A Secondary Metabolite Profile From Roots And Leaves Of Iostephane Heterophylla By Uplc-Ms And Gc-Ms, Diana V. Navarrete-Carriola, Alma D. Paz-González, Lenci K. Vázquez-Jiménez, Erick De Luna-Santillana, María A. Cruz-Hernández, Debasish Bandyopadhyay, Gildardo Rivera

School of Integrative Biological & Chemical Sciences Faculty Publications

Iostephane heterophylla is a traditional Mexican medicinal plant and is an important source of secondary metabolites with antimicrobial and cytotoxic activity. The aim of this work was to conduct a comparative analysis of secondary metabolites of different roots and leaf extracts of I. heterophylla from two zones in Mexico using ultraperformance liquid chromatography (UPLC) and gas chromatography (GC) coupled with mass spectrometry (MS). Twelve secondary metabolites from roots were identified in the leaves. Five new molecular weight secondary metabolites not previously reported were found. Six bioactive metabolites were quantified (quercetin ≤0.151 mg/mL in root and ≤0.041 mg/mL in leaf; hesperidin …

Comparative Animal Mucomics, Antonio R. Cerullo

Dissertations, Theses, and Capstone Projects

Mucus is one of Nature’s most abundant and versatile biomaterials. These secretions are present in all animals, from the lowly garden snail to the great blue whale, and fulfill a multitude of functions, acting as antimicrobial barriers, moisturizers, adhesive glues, surface lubricants, and mineralizing agents. Despite their importance, very little is known about mucus compositions or properties. The largest challenge precluding the greater understanding of mucus function is its complexity; a single mucus contains complex mixtures of proteins, glycans, and ions that all have important roles in function. Therefore, understanding mucus function necessitates analysis that compares different mucus from one …

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 …

Mechanistic And Engineering Studies Of Lov Photoreceptors In Yeast, Matthew M. Cleere

Dissertations, Theses, and Capstone Projects

A variety of cellular biosensors have evolved which can translate electromagnetic radiation from the environment into biological functions. Light-Oxygen-Voltage (LOV) domains in particular, are a group of photoreceptors that respond to blue wavelengths of light and can become a cellular photoswitch by converting this stimulus through their attached effector domains. For instance, the Helix-Turn-Helix (HTH) DNA-binding activity of the bacterial transcription factor EL222 and the Regulator of G-protein Signaling (RGS) in the fungal membrane associating protein BcLOV4 are both induced by blue-light sensing LOV domains. While previous work has provided the field with a structural characterization of LOV proteins in …

Rational Design Of Peptide-Based Materials Informed By Multiscale Molecular Dynamics Simulations, Dhwanit Rahul Dave

Dissertations, Theses, and Capstone Projects

The challenge of establishing a sustainable and circular economy for materials in medicine and technology necessitates bioinspired design. Nature's intricate machinery, forged through evolution, relies on a finite set of biomolecular building blocks with through-bond and through-space interactions. Repurposing these molecular building blocks requires a seamless integration of computational modeling, design, and experimental validation. The tools and concepts developed in this thesis pioneer new directions in peptide-materials design, grounded in fundamental principles of physical chemistry. We present a synergistic approach that integrates experimental designs and computational methods, specifically molecular dynamics simulations, to gain in-depth molecular insights crucial for advancing the …

Biomolecular Crystals As Functional Materials, Fahmeed Khan Sheehan

Dissertations, Theses, and Capstone Projects

The field of supramolecular chemistry has undergone significant evolution over the last few decades, progressing from fundamental studies of self-assembling systems to the rational design of functional materials with exceptional properties. Among these materials, short peptides have emerged as a chemically simple yet highly versatile class of biomimetic compounds. Initially, short peptides were used as model systems to understand larger protein interactions. As the field progressed, short peptides were found to have exceptional functionality, and are now explored as functional nanomaterials for diverse applications. In many cases, short peptide materials have displayed properties not found in biology, in some cases …

Studying The Genes And Conditions That Influence Root Development, Tessa Holtkamp, Hannah Ordonez Webb

Undergraduate Research Symposium

Root development in plants is essential for their survival and understanding how hormones influence their development can explain how plants grow under different circumstances. Researching how Indole-3-butyric acid (IBA), a hormone that induces root production, affects the plant model Arabidopsis thaliana helps explain the hormone's effect in agricultural crop systems. To understand root pathways, we performed assays on mutant lines of Arabidopsis by growing plants on varying concentrations of IBA. For wild-type and mutant lines, phenotyping experiments like branching of roots, lengths of stems, and root length were conducted along with PCR and restriction digest genotyping experiments to compare their …

Investigation Of Alzheimer’S Amyloid-Β Protein Aggregation With A New Fluorescent Dye., Emma Alberty

Undergraduate Research Symposium

Alzheimer’s Disease (AD) is the most common form of dementia characterized by the impairment of at least two brain functions such as memory loss and judgement. AD is a progressive illness that can last as many as 20 years. AD is largely considered to be caused by the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. A better understanding of the structure and function of these plaques may lead to clearer understanding of the disease. To analyze amyloid plaques, aggregation assays are often used. During these assays we begin with monomer and place the sample in biological conditions to …

Chromosome‑Level Assembly And Analysis Of Camelina Neglecta: A Novel Diploid Model For Camelina Biotechnology Research, Shuo Wang, Rostislav Y. Blume, Zhi‑Wei Zhou, Shaoping Lu, Tara J. Nazarenus, Yaroslav B. Blume, Weibo Xie, Edgar B. Cahoon, Ling‑Ling Chen, Liang Guo

Department of Biochemistry: Faculty Publications

Camelina neglecta is a new diploid Brassicaceae species, which has great research value because of its close relationship with the hexaploid oilseed crop Camelina sativa. Here, we report a chromosome-level assembly of C. neglecta with a total length of 210 Mb. By adopting PacBio sequencing and Hi-C technology, the C. neglecta genome was assembled into 6 chromosomes with scaffold N50 of 29.62 Mb. C. neglecta has undergone the whole-genome triplication (γ) shared among eudicots and two whole-genome duplications (α and β) shared by crucifers, but it has not undergone a specific whole-genome duplication event. By synteny analysis …