Digital Commons Network^™

Discovery Of Ro 41-0960, A Non-Steroidal Inhibitor Of The Na+/K+-Atpase, Carlos Cruz-Cortés, Jaroslava Šeflová, Guadalupe Guerrero-Serna, Eric N. Jimenez-Vazquez

Health & Biomedical Sciences Faculty Publications

The Na⁺/K⁺-ATPase (NKA) is a central regulator of cardiac ion homeostasis and a validated target for heart failure. Yet, cardiotonic steroids used in clinical practice are limited by a narrow therapeutic window and pro-arrhythmic effects. Here, we identify Ro 41-0960 as a non-steroidal inhibitor of NKA with a distinct mechanistic profile. The compound inhibits NKA activity with IC50 values of 17.9 ± 1.1 µM for purified enzyme and https://doi.org/10.3 ± 1.1 µM in microsomal preparations. ATP-dependent activity measurements revealed a non-monotonic response in which inhibition was most pronounced at ATP concentrations below 4 mM and diminished …

Norman H. Cromwell, Unl Chemistry; Nu System Dean; Eppley Cancer Center Director, Norman H. Cromwell, Pete Boughn, Mark A. Griep

UNL ORCA Interview Series

This 1980 interview of Normal Cromwell was done by Pete Boughn at the University of Nebraska Medical Center in Omaha. He asked about Cromwell’s history but mostly about his time as director of the Eppley Cancer Center. The interview is reproduced with permission from the UNMC McGoogan Library.

Cromwell was born in 1913 in Terre Haute, Indiana. In 1935, he earned a bachelor’s degree in chemical engineering from the Rose-Hulman Institute of Technology in his hometown. In 1939, three things happened: he earned a doctorate in organic chemistry from the University of Minnesota, he got married, and he was hired …

Identification Of Active Compounds And Antidiabetic Activity Of Red Shoot (Syzygium Myrtifolium) Leaves Extract With In Vitro And In Silico Methods, Muhamad Iqbal Prakoso, Siti Warnasih

Pharmaceutical Sciences and Research

Diabetes mellitus (DM) is a chronic metabolic disease that affects approximately 537 million people worldwide (1 in 10 individuals), and its prevalence is projected to reach 783 million by 2045. One of the plants that has the potential to be an antidiabetic is red shoots (Syzygium myrtifolium) since it contains various secondary metabolite compounds such as flavonoids, triterpenoids, steroids, saponins, phenolics, and anthocyanins. This study aimed to evaluate the antidiabetic properties of red shoot leaves extract and to identify and predict interactions between its active compounds and the α-glucosidase receptor. Ethanol, ethyl acetate, and n-hexane extracts of red …

Sustained Response To Pan-Braf Inhibitor Plixorafenib (Fore8394, Plx8394) In A Young Adult With Neurodegenerative Langerhans Cell Histiocytosis, Joanna S Yi, Kathleen S Mccarthy, Kate Mazur, Rebecca Kudlaty, Terry Armstrong, Nilesh Desai, Stacie Peacock Shepherd, Daniel Zinn, Jessica Velazquez, Brooks Scull, Carl Allen, Kenneth Mcclain

Faculty, Staff and Students Publications

No abstract provided.

Synthesis, Structure-Activity Relationships, And Antitumor Activities Of Quinoxiline-Containing Inhibitors Of The Protein-Protein Interactions Between Transcription Coactivator Af9/Enl And Dot1l/Af4, Chandra Bhushan Mishra, Xin Li, Bala Krishna Moku, Sehun Kwak, Dnyaneshwar N Garad, Yongcheng Song

Faculty, Staff and Students Publications

Mixed lineage leukemia (MLL) gene rearrangements cause ~75% of acute leukemia in infants and 5-10% in children and adults with poor clinical outcomes. Protein-protein interactions (PPI) between frequent MLL fusion partners AF9/ENL and AF4 or histone methyltransferase DOT1L are drug targets for MLL-rearranged (MLL-r) leukemia. Sixty-seven quinoxiline compounds were synthesized and tested for their ability to inhibit such PPIs. Compounds 16, 17, 59 and 63 were found to be potent inhibitors with IC50 values of 0.35-1.5 μM. Structure-activity relationships are discussed. Potent inhibitors can suppress expression of MLL target genes Myc and Meis1 and selectively block proliferation of MLL-r and …

Lung-Delivered Il-10 Mitigates Lung Inflammation Induced By Repeated Endotoxin Exposures In Male Mice, Aaron Schwab, Todd A. Wyatt, Oliver Schanze, Amy J. Nelson, Angela Gleason, Michael J. Duryee, Deanna Mosley, Geoffrey M. Thiele, Ted R. Mikuls, Jill A. Poole

Journal Articles: Environmental, Agricultural & Occupational Health

Therapies capable of resolving inflammatory lung disease resulting from high-consequence occupational/environmental hazards are lacking. This study seeks to determine the therapeutic potential of direct lung-delivered interleukin (IL)-10 following repeated lipopolysaccharide exposures. C57BL/6 mice were intratracheally instilled with LPS (10 μg) and treated with IL-10 (1 μg) or vehicle control for 3 days. Lung cell infiltrates were enumerated by flow cytometry. Lung sections were stained for myeloperoxidase (MPO), CCR2, vimentin, and post-translational protein citrullination (CIT) and malondialdehyde-acetaldehyde (MAA) modifications. Lung function testing and longitudinal in vivo micro-CT imaging were performed. Whole lungs were profiled using bulk RNA sequencing. IL-10 treatment reduced …

Cellular And Behavioral Consequences Of Psychedelic Drug Action In The Claustrum, Tanner L. Anderson

Theses and Dissertations--Neuroscience

Psychedelics are rapidly garnering research attention for their ability to successfully treat a variety of psychiatric diseases after one or a handful of treatments in recent clinical research. Among the conditions treated is substance use disorder (SUD), which afflicted 48.5 million (16.7%) Americans aged 12 and older in 2023 (NSDUH). As clinical trial results continue to show lasting positive effects of psychedelic psychotherapy, there remains an enormous gap in knowledge regarding how these drugs cause lasting changes in the brain to achieve these therapeutic effects. It has been suggested that psychedelics must induce rapid and long-lasting neuronal plasticity in order …

Design And Development Of Fluorescent Probes For Sensing And Bioimaging Of Nad(P)H, Intracellular Viscosity, And So2, Dilka Liyana Arachchige

Dissertations, Master's Theses and Master's Reports

Understanding the dynamic biochemical and biophysical changes within living systems is vital for advancing disease diagnosis and therapeutic development. This work presents the design and development of innovative fluorescent probes, based on cyanine and coumarin scaffolds, for the highly sensitive and selective detection of key metabolic and biophysical markers, NAD(P)H, mitochondrial viscosity, and sulfur dioxide (SO₂) in live cells and fruit fly larvae. A series of cyanine-based probes were engineered to undergo strong fluorescence enhancement upon reduction by NAD(P)H, enabling real-time visualization of metabolic fluctuations in cancer cells and Drosophila larvae. These probes exhibit excellent sensitivity, mitochondrial targeting capability, and …

Effect Of Inulin From Dahlia Tubers (Dahlia Variabilis) Extract On Insulitis Severity And Insulin Expression In Diabetic Rats, Ismawati Ismawati, Saryono Saryono, Mukhyarjon Mukhyarjon, Ilhami Romus, Veni Dayu Putri, Sri Yanti, Fitri Dyna, Nada Idzdihari Adesti

BioMedicine

Background: Dahlia (Dahlia variabilis), a widely cultivated ornamental plant in Indonesia, is known to contain 84.08% inulin in its tubers. Numerous studies have demonstrated the antidiabetic potential of inulin from various plant sources. However, most of the research is in the form of a mixture of inulin with other active substances, and no one has analyzed the effects of inulin derived from dahlia tubers. This study examines the effect of inulin from dahlia tuber extract on blood glucose levels, serum insulin expression, pancreatic tissue insulin expression, homeostatic model assessment of insulin resistance (HOMA-IR), and the extent of …

Enhanced Ctla-4 Blockade Anti-Tumor Immunity With Apg-157 Combination In A Murine Head And Neck Cancer, Daniel Sanghoon Shin, Saroj Basak, Mysore S Veena, Begoña Comin-Anduix, Arjun Bhattacharya, Tien S Dong, Albert Ko, Philip Han, Jonathan Jacobs, Neda A Moatamed, Luis Avila, Matteo Pellegrini, Marilene Wang, Eri S Srivatsan

Faculty, Staff and Student Publications

BACKGROUND: A phase I clinical study for patients with locally advanced H&N cancer with a new class of botanical drug APG-157 provided hints of potential synergy with immunotherapy. We sought to evaluate the efficacy of the combination of APG-157 and immune checkpoint inhibitors.

METHODS: CCL23, UM-SCC1 (human), and SCCVII (HPV-), MEER (HPV+) (murine) H&N cancer cell lines were utilized for in vitro and in vivo studies. We measured tumor growth by treating the mice with APG-157, anti-PD-1, and anti-CTLA-4 antibody combinations (8 groups). The tumor microenvironments were assessed by multi-color flow cytometry, immunohistochemistry, and RNA-seq analysis. Fecal microbiome was analyzed …

Discovery Of Strong 3-Nitro-2-Phenyl-2h-Chromene Analogues As Antitrypanosomal Agents And Inhibitors Of Trypanosoma Cruzi Glucokinase, Shane M. Carey, Destiny M. O’Neill, Garrett B. Conner, Julian Sherman, Ana Rodriguez, Edward L. D'Antonio

Natural Sciences Faculty Publications

Chagas disease is one of the world’s neglected tropical diseases, caused by the human pathogenic protozoan parasite Trypanosoma cruzi. There is currently a lack of effective and tolerable clinically available therapeutics to treat this life-threatening illness and the discovery of modern alternative options is an urgent matter. T. cruzi glucokinase (TcGlcK) is a potential drug target because its product, D-glucose-6-phosphate, serves as a key metabolite in the pentose phosphate pathway, glycolysis, and gluconeogenesis. In 2019, we identified a novel cluster of TcGlcK inhibitors that also exhibited anti-T. cruzi efficacy called the 3-nitro-2-phenyl-2H-chromene analogues. This was achieved by performing a target-based …

Recurrent Lymphoid And Myeloid Relapses Due To Treatment Cessations Reveal Natural History Of Ph-Positive B-All And Pose A Diagnostic Challenge, Shimin Hu, Elias J Jabbour, Collin Y Hu, Guilin Tang, Wei Wang, L Jeffrey Medeiros, Carlos Bueso-Ramos

Faculty, Staff and Student Publications

No abstract provided.

Design Of Two New Sulfur Derivatives Of Perezone: In Silico Study Simulation Targeting Parp-1 And In Vitro Study Validation Using Cancer Cell Lines, Alejandro Rubiales-Martínez, Joel Martinez, Elvia Mera-Jiménez, Javier Perez-Flores, Guillermo Tellez-Isaias, Rene Miranda Ruvacalba, Maricarmen Hernandez-Rodriguez, Teresa Mancillo Percino, Martha Edith Macia Perez, Maria Ines Nicholas-Vazquez

Poultry Science Faculty Publications and Presentations

Poly-ADP-Ribose Polymerase (PARP-1) is an overexpressed enzyme in several carcinomas; consequently, the design of PARP-1 inhibitors has acquired special attention. Hence, in the present study, three compounds (8–10) were produced through a Michael addition protocol, using phenylmethanethiol, 5-fluoro-2-mercaptobenzyl alcohol, and 4-mercaptophenylacetic acid, respectively, as nucleophiles and perezone as the substrate, expecting them to be convenient candidates that inhibit PARP-1. It is convenient to note that in the first stage of the whole study, the molecular dynamics (MD) simulations and the quantum chemistry studies of four secondary metabolites, i.e., perezone (1), perezone angelate (2 …

Efficacy Of Gonacon Fertility Control Against Prairie Dogs And Potential For Uses On Other Rodent Species, Aaron B. Shiels, Emily W. Ruell, Jason E. Bruemmer

United States Department of Agriculture Wildlife Services: Staff Publications

Use of a contraceptive (i.e., fertility control) is attractive for rodent management where lethal control is unwanted. Although population reduction is generally unachievable with small-scale, short-term contraceptive use, reduced juvenile recruitment is achievable. The injectable immunocontraceptive vaccine GonaCon (active ingredient: gonadotropin releasing hormone [GnRH]) was registered in 2022 by the United States Environmental Protection Agency (EPA) for controlling fertility of female prairie dogs (Cynomys, a type of ground squirrel) in urban/suburban settings. Here we: 1) describe past research, including a replicated field study in Colorado (GonaCon treatment vs. control sites) testing efficacy of GonaCon in prairie dogs, which …

Discovery, Structure-Activity Relationship And In Vitro Anticancer Activity Of Small-Molecule Inhibitors Of The Protein-Protein Interactions Between Af9/Enl And Af4 Or Dot1l, Xin Li, Xiaowei Wu, Shenyou Nie, Jidong Zhao, Yuan Yao, Fangrui Wu, Chandra Bhushan Mishra, Md Ashraf-Uz-Zaman, Bala Krishna Moku, Yongcheng Song

Faculty, Staff and Students Publications

Simple Summary

Chromosomal translocations involving the mixed lineage leukemia (MLL) gene generate potent fusion oncogenes and cause acute myeloid leukemia or lymphocytic leukemia, which account for ~75% infant and 5–10% child/adult acute leukemia cases with a poor prognosis (5-year survival rates < 45%). Protein–protein interactions between the most frequent MLL fusion partner proteins AF9/ENL and AF4 or histone methyltransferase DOT1L are critical to malignant gene expression and are therefore a potential drug target for cancer. Compound screening followed by medicinal chemistry studies identified several novel small-molecule inhibitors showing strong inhibition of these protein–protein interactions, significant suppression of characteristic gene expression, and robust cellular anticancer activities with negligible cytotoxicity. These compounds are useful chemical probes for biological studies of these protein–protein interactions, as well as pharmacological leads for further drug development against MLL-rearranged and other leukemias.

Abstract

Chromosomal translocations involving the mixed lineage leukemia (MLL) gene cause 5–10% acute leukemias with poor clinical outcomes. Protein–protein interactions (PPI) between the most frequent MLL fusion partner proteins AF9/ENL and AF4 or histone methyltransferase DOT1L are drug targets for MLL-rearranged (MLL-r) leukemia. Several benzothiophene-carboxamide compounds were identified as novel inhibitors of these PPIs with IC₅₀ values as …

Identification Of A Β-Arrestin-Biased Negative Allosteric Modulator For The Β2-Adrenergic Receptor, Michael Ippolito, Francesco De Pascali, Nathan Hopfinger, Konstantin E. Komolov, Daniela Laurinavichyute, Poli Adi Narayana Reddy, Leon A. Sakkal, Kyle Z. Rajkowski, Ajay P. Nayak, Justin Lee, Jordan Lee, Gaoyuan Cao, Preston S. Donover, Melvin Reichman, Stevens. An, Joseph M. Salvino, Raymond B. Penn, Roger S S. Armen, Charles P. Scott, Jeffrey L. Benovic

Department of Biochemistry and Molecular Biology Faculty Papers

Catecholamine-stimulated β2-adrenergic receptor (β2AR) signaling via the canonical Gs–adenylyl cyclase–cAMP–PKA pathway regulates numerous physiological functions, including the therapeutic effects of exogenous β-agonists in the treatment of airway disease. β2AR signaling is tightly regulated by GRKs and β-arrestins, which together promote β2AR desensitization and internalization as well as downstream signaling, often antithetical to the canonical pathway. Thus, the ability to bias β2AR signaling toward the Gs pathway while avoiding β-arrestin-mediated effects may provide a strategy to improve the functional consequences of β2AR activation. Since attempts to develop Gs-biased agonists and allosteric modulators for the β2AR have been largely unsuccessful, here we …

Slo3 In The Fast Lane: The Latest Male Contraceptive Target With A Promising Small-Molecule Inhibitor, Zhi Tan, Thomas X Garcia

Faculty, Staff and Students Publications

No abstract provided.

Deposited Cigarette Smoke As A Driver Of Oxidation And Partitioning Processes On Indoor Surfaces, April Hurlock

Honors Theses

Despite the large amount of time that individuals spend indoors during their lives, very little attention was paid to the chemistry that occurs on indoor surfaces until recently. Although not visible to the naked eye, physical and chemical processes, such as partitioning and oxidation, are occurring on virtually every indoor surface in a typical household. Indoor pollutants, ranging from skin oils to environmental cigarette smoke, drive a lot of these processes. The transformation of indoor surfaces by indoor pollutants can increase chemical exposure risks as new irritants or carcinogens can be introduced to the surfaces. In this thesis, I describe …

Induction Of Antibiotic Activity Against Methicillin-Resistant Staphylococcus Aureus In Small Molecules Through Zinc Activation, Rachel Michaela Andrews

All ETDs from UAB

Methicillin-resistant Staphylococcus aureus (MRSA) is a serious human pathogen with a staggering potential for multi-drug resistance. Because of this, the Centers for Disease Control and Prevention and the World Health Organization monitor the spread of MRSA and encourage antibiotic development efforts targeting this pathogen. Despite this, few antibiotics have been developed and brought to market in recent decades. To continue treating infections caused by this organism, we must identify novel antibiotic molecules with different mechanisms of action from known antibiotics. Bacterial copper-dependent inhibitors (CDIs), molecules that become antibacterial in the presence of copper (Cu), have been studied as a novel …

Far-Uvc: Technology Update With An Untapped Potential To Mitigate Airborne Infections, P. Jacob Bueno De Mesquita, Rosemary K. Sokas, Mary B. Rice, Edward A. Nardell

Arts & Sciences Faculty Publications

No abstract provided.

Structure-Activity Relationship And Antitumor Activity Of 1,4-Pyrazine-Containing Inhibitors Of Histone Acetyltransferases P300/Cbp, Shenyou Nie, Fangrui Wu, Jingyu Wu, Xin Li, Chao Zhou, Yuan Yao, Yongcheng Song

Faculty, Staff and Students Publications

Acetylation of histone lysine residues by histone acetyltransferase (HAT) p300 and its paralog CBP play important roles in gene regulation in health and diseases. The HAT domain of p300/CBP has been found to be a potential drug target for cancer. Compound screening followed by structure-activity relationship studies yielded a novel series of 1,4-pyrazine-containing inhibitors of p300/CBP HAT with their IC50s as low as 1.4 μM. Enzyme kinetics and other studies support the most potent compound 29 is a competitive inhibitor of p300 HAT against the substrate histone. It exhibited a high selectivity for p300 and CBP, with negligible activity on …

All In: How Colby Met Covid-19, Gerry Boyle

Colby Magazine

It was last August and first-years were arriving, unloading cars, lugging stuff into residence halls. President David A. Greene was on hand for the big day, meeting students, greeting parents, only to hear, “We expect to be back here within two weeks to a month to pick up our child.” It didn’t happen.

Development Of A Novel Vertebrate Pesticide For The Invasive Small Indian Mongoose, Carmen Antaky, Steven C. Hess, Israel Leinbach, Robert T. T. Sugihara, Emily W. Ruell, Shane Siers

United States Department of Agriculture Wildlife Services: Staff Publications

Small Indian mongooses are detrimental introduced predators in the United States, where they depredate native species, serve as vector of disease, and threaten public safety. Due to the risk of accidental introduction to mongoose-free islands, high cost and limitations to trapping, and no national (Section 3) Environmental Protection Agency (EPA)-registered toxicants for mongoose control, there is a need for an efficacious toxic bait for mongooses for use in conservation areas and at points of entry in the United States. Over the last five years, the National Wildlife Research Center (NWRC) worked to develop a toxic bait for mongooses for registration …

Unintended Consequences Of Air Cleaning Chemistry, Douglas B. Collins, Delphine K. Farmer

Faculty Journal Articles

Amplified interest in maintaining clean indoor air associated with the airborne transmission risks of SARS-CoV-2 have led to an expansion in the market for commercially available air cleaning systems. While the optimal way to mitigate indoor air pollutants or contaminants is to control (remove) the source, air cleaners are a tool for use when absolute source control is not possible. Interventions for indoor air quality management include physical removal of pollutants through ventilation or collection on filters and sorbent materials, along with chemically reactive processes that transform pollutants or seek to deactivate biological entities. This perspective intends to highlight the …

Thioredoxin Reductase Is A Major Regulator Of Metabolism In Leukemia Cells, Sheelarani Karunanithi, Ruifu Liu, Yongchun Hou, Giancarlo Gonzalez, Natasha Oldford, Anne Jessica Roe, Nethrie Idipilly, Kalpana Gupta, Chandra Sekhar Amara, Satwikreddy Putluri, Grace Kyueun Lee, Juan Valentin-Goyco, Lindsay Stetson, Stephen A Moreton, Vasanta Putluri, Shyam M Kavuri, Yogen Saunthararajah, Marcos De Lima, Gregory P Tochtrop, Nagireddy Putluri, David N Wald

Faculty, Staff and Students Publications

Despite the fact that AML is the most common acute leukemia in adults, patient outcomes are poor necessitating the development of novel therapies. We identified that inhibition of Thioredoxin Reductase (TrxR) is a promising strategy for AML and report a highly potent and specific inhibitor of TrxR, S-250. Both pharmacologic and genetic inhibition of TrxR impairs the growth of human AML in mouse models. We found that TrxR inhibition leads to a rapid and marked impairment of metabolism in leukemic cells subsequently leading to cell death. TrxR was found to be a major and direct regulator of metabolism in AML …

Structure, Function And Inhibition Of Critical Protein-Protein Interactions Involving Mixed Lineage Leukemia 1 And Its Fusion Oncoproteins, Xin Li, Yongcheng Song

Faculty, Staff and Students Publications

Mixed lineage leukemia 1 (MLL1, also known as MLL or KMT2A) is an important transcription factor and histone-H3 lysine-4 (H3K4) methyltransferase. It is a master regulator for transcription of important genes (e.g., Hox genes) for embryonic development and hematopoiesis. However, it is largely dispensable in matured cells. Dysregulation of MLL1 leads to overexpression of certain Hox genes and eventually leukemia initiation. Chromosome translocations involving MLL1 cause ~ 75% of acute leukemia in infants and 5-10% in children and adults with a poor prognosis. Targeted therapeutics against oncogenic fusion MLL1 (onco-MLL1) are therefore needed. Onco-MLL1 consists of the N-terminal DNA-interacting domains …

Synthesis, Structure-Activity Relationships, And Antiviral Activity Of Allosteric Inhibitors Of Flavivirus Ns2b-Ns3 Protease, Shenyou Nie, Yuan Yao, Fangrui Wu, Xiaowei Wu, Jidong Zhao, Yuanda Hua, Jingyu Wu, Tong Huo, Yi-Lun Lin, Alexander R Kneubehl, Megan B Vogt, Josephine Ferreon, Rebecca Rico-Hesse, Yongcheng Song

Faculty, Staff and Students Publications

Flaviviruses, including Zika, dengue and West Nile virus, are important human pathogens. The highly conserved NS2B-NS3 protease of Flavivirus is essential for viral replication and therefore a promising drug target. Through compound screen followed by medicinal chemistry studies, a novel series of 2,5,6-trisubstituted pyrazine compounds are found to be potent, allosteric inhibitors of Zika virus protease (ZVpro) with IC50 values as low as 130 nM. Their structure-activity relationships are discussed. The ZVpro inhibitors also inhibit homologous proteases of dengue and West Nile virus and their inhibitory activities are correlated. The most potent compounds 47 and 103 potently inhibited Zika virus …

Small-Molecule Inhibitor Of Af9/Enl-Dot1l/Af4/Aff4 Interactions Suppresses Malignant Gene Expression And Tumor Grow, Fangrui Wu, Shenyou Nie, Yuan Yao, Tong Huo, Xin Li, Xiaowei Wu, Jidong Zhao, Yi-Lun Lin, Yinjie Zhang, Qianxing Mo, Yongcheng Song

Faculty, Staff and Students Publications

Chromosome translocations involving mixed lineage leukemia (MLL) gene cause acute leukemia with a poor prognosis. MLL is frequently fused with transcription cofactors AF4 (~35%), AF9 (25%) or its paralog ENL (10%). The AHD domain of AF9/ENL binds to AF4, its paralog AFF4, or histone-H3 lysine-79 (H3K79) methyltransferase DOT1L. Formation of AF9/ENL/AF4/AFF4-containing super elongation complexes (SEC) and the catalytic activity of DOT1L are essential for MLL-rearranged leukemia. Protein-protein interactions (PPI) between AF9/ENL and DOT1L/AF4/AFF4 are therefore a potential drug target.

Methods: Compound screening followed by medicinal chemistry was used to find inhibitors of such PPIs, which were examined for their biological …

Zinc Finger Dna Repair Protein Targets Of Arsenite In The Nucleotide Excision Repair Pathway, Juliana M. Huestis

Biomedical Sciences ETDs

Environmental arsenic exposure affects around 100 million people worldwide. Recent evidence shows that arsenite, even at low concentrations, may act as a co-carcinogen, by displacing zinc from the zinc finger motifs of certain DNA repair proteins, leaving them vulnerable to redox modification and loss of protein function. This study probes the physical chemistry underlying arsenite and zinc binding to XPA and PARP1, in the hope of illuminating some of the aspects of protein structure that determine susceptibility to arsenite binding. In this study, dissociation constants are determined for zinc and arsenite binding to peptides corresponding to the C4 zinc finger …

Alternatives To Red Blood Cell Transfusions, Julia Prosser

Capstone Showcase

Abstract

Introduction: Allogenic red blood cell (RBC) transfusions are used for a number of different reasons. As with any medical procedure, allogenic RBC transfusions are not risk-free. Since the first recorded blood transfusion in 1655, the process has remained relatively unchanged. ABO incompatibility and contamination with infectious diseases are two major complications associated with RBC transfusions. Furthermore, traditional allogenic RBC transfusions have supply and demand issues. These issues, plus several more, could be alleviated with the use of artificial blood. This paper addresses the important clinical question: In patients who require RBC transfusions (P), is there a viable artificial blood …