Life Sciences Commons^™

Investigation Of Cofactor Activities Of Endothelial Microparticle- Thrombomodulin With Liposomal Surrogate, Valentinas Gruzdys, Lin Wang, Dan Wang, Rachel Huang, Xue-Long Sun

Chemistry Faculty Publications

Thrombomodulin (TM) is a type I transmembrane glycoprotein mainly expressed on the endothelial cells, where it binds thrombin to form the thrombin-TM complex that can activate protein C and thrombin-activable fibrinolysis inhibitor (TAFI) and induce anticoagulant and anti-fibrinolytic reactions, respec-tively. Cell activation and injury often sheds microparticles that contain membrane TM, which circulate in biofluids like blood. However, the biological function of circulating microparticle-TM is still unknown even though it has been recognized as a biomarker of endothelial cell injury and damage. In comparison with cell membrane, different phospholipids are exposed on the microparticle surface due to cell membrane "flip-flop"upon …

Nucleobase-Modified Nucleosides And Nucleotides: Applications In Biochemistry, Synthetic Biology, And Drug Discovery, Anthony J. Berdis

Chemistry Faculty Publications

DNA is often referred to as the "molecule of life " since it contains the genetic blueprint for all forms of life on this planet. The core building blocks composing DNA are deoxynucleotides. While the deoxyribose sugar and phosphate group are ubiquitous, it is the composition and spatial arrangement of the four natural nucleobases, adenine (A), cytosine (C), guanine (G), and thymine (T), that provide diversity in the coding information present in DNA. The ability of DNA to function as the genetic blueprint has historically been attributed to the formation of proper hydrogen bonding interactions made between complementary nucleobases. However, …

Targeting Heat Shock 27 Kda Protein Induces Androgen Receptor Degradation, Yaxin Li

ETD Archive

Glioblastoma (GBM) is the most common and aggressive brain tumor, with very poor prognosis. Androgen receptor (AR) plays a significant role in the progression of GBM, and anti-androgen agents have the potential to be used for the treatment of GBM. However, AR mutation commonly happens in GBM, which makes the anti-androgen agents less effective. Heat shock 27 kDa protein (HSP27) is a well-documented chaperone protein to stabilize AR. Inhibition of HSP27 results in AR degradation regardless the mutation status of AR, which makes HSP27 a good target to abolish AR in GBM. Identified compound I ((N-(3-((2,5-dimethoxybenzyl)oxy)-4-(methylsulfonamido) phenyl)-4-methoxybenzamide) inhibits GBM cell …

Pharyngeal Constriction As A Cause For Late Acquisition And Speech Sound Disorders Of Rhotic Sounds In English, Spanish, And French, Connor Mahon

The Downtown Review

This paper attempts to explain why rhotic sounds are cross-linguistically late developing among the sound inventory of children. Included is a summary of the current literature regarding classification of rhotic sounds, an examination of the articulatory movement of the tongue root, and an overview of the clinical implications on the field of speech-language pathology. The evidence presented supports the hypothesis that pharyngeal constriction is characteristic of rhotic sounds in many languages, and that it is related to the relative late acquisition and higher rate of speech sound disorders, as seen in English, Spanish, and French.

An Agent-Based Simulator For The Gastrointestinal Pathway Of Listeria Monocytogenes, Ashrafur Rahman, Ali Asgary, Daniel Munther, Aamir Fazil, Ben A. Smith, Jianhong Wu

Mathematics and Statistics Faculty Publications

We developed an agent-based gastric simulator for a human host to illustrate the within host survival mechanisms of Listeria monocytogenes. The simulator incorporates the gastric physiology and digestion processes that are critical for pathogen survival in the stomach. Mathematical formulations for the pH dynamics, stomach emptying time, and survival probability in the presence of gastric acid are integrated in the simulator to evaluate the portion of ingested bacteria that survives in the stomach and reaches the small intestine. The parameters are estimated using in vitro data relevant to the human stomach and L. monocytogenes. The simulator predicts that 5%–29% of …

Towards Enhanced Chlorine Control: Mathematical Modeling For Free Chlorine Kinetics During Fresh-Cut Carrot, Cabbage And Lettuce Washing, Parthasarathy Srinivasan, Mohammadreza Dehghan Abnavi, Anthony Sulak, Chandrasekhar R. Kothapalli, Daniel Munther

Mathematics and Statistics Faculty Publications

In this study, we developed a novel produce-specific mechanistic model to predict free chlorine (FC) dynamics during washing of disk-cut carrots, cut cabbage, and cut iceberg lettuce, in 3 L and 50–100 L tanks, and of shredded iceberg lettuce in 3200 L pilot-plant trials. Ranges for two key parameters: β (L mg−1 min−1) the apparent reaction rate constant of FC with produce constituents, and γ, the fraction of the increase of chemical oxygen demand (COD) contributing to the reaction, were determined at the 3 L scale. For disk carrots β∈[0.05,0.09] and γ∈[0.054,0.078], for cut cabbage β∈[0.05,0.10] and γ∈[0.09,0.12], and for …

Enhancing Produce Safety: State Estimation-Based Robust Adaptive Control Of A Produce Wash System, Vahid Azimi, Daniel Munther, Mojtaba Sharifi, Patricio A. Vela

Mathematics and Statistics Faculty Publications

The rapid introduction of fresh-cut produce into a produce wash system can dramatically decrease the free chlorine (FC) concentration level in the wash water, resulting in potential widespread cross-contamination throughout the entire wash system. To minimize such contamination, a sufficient level of FC must be maintained in the wash water. This paper presents a state estimation-based robust adaptive sliding mode (RASM) control strategy for the wash system to stabilize the FC concentration level during fresh-cut iceberg lettuce washing. This feedback control law for FC dosing is suggested to provide a sufficient FC injection rate (FCIR) to the wash system in …

Formation Of Escherichia Coli O157: H7 Persister Cells In The Lettuce Phyllosphere And Application Of Differential Equation Models To Predict Their Prevalence On Lettuce Plants In The Field, Daniel S. Munther, Michelle Q. Carter, Claude V. Aldric, Renata Ivanek, Maria T. Brandl

Mathematics and Statistics Faculty Publications

American Society for Microbiology. Escherichia coli O157:H7 (EcO157) infections have been recurrently associated with produce. The physiological state of EcO157 cells surviving the many stresses encountered on plants is poorly understood. EcO157 populations on plants in the field generally follow a biphasic decay in which small subpopulations survive over longer periods of time. We hypothesized that these subpopulations include persister cells, known as cells in a transient dormant state that arise through phenotypic variation in a clonal population. Using three experimental regimes (with growing, stationary at carrying capacity, and decaying populations), we measured the persister cell fractions in culturable EcO157 …

Modeling Of Free Chlorine Consumption And Escherichia Coli O157:H7 Cross-Contamination During Fresh-Cut Produce Wash Cycles, Mohammadreza Dehghan Abnavi, Ali Alradaan, Daniel Munther, Chandrasekhar R. Kothapalli, Partha Srinivasan

Mathematics and Statistics Faculty Publications

Controlling the free chlorine (FC) availability in wash water during sanitization of fresh produce enhances our ability to reduce microbial levels and prevent cross-contamination. However, maintaining an ideal concentration of FC that could prevent the risk of contamination within the wash system is still a technical challenge in the industry, indicating the need to better understand wash water chemistry dynamics. Using bench-scale experiments and modeling approaches, we developed a comprehensive mathematical model to predict the FC concentration during fresh-cut produce wash processes for different lettuce types (romaine, iceberg, green leaf, and red leaf), carrots, and green cabbage as well as …

Shifts In Plant Functional Composition Following Long-Term Drought In Grasslands, Robert J. Griffin‐Nolan, Dana M. Blumenthal, Scott L. Collins, Timothy E. Farkas, Ava M. Hoffman, Kevin E. Mueller, Troy W. Ocheltree, Melinda D. Smith, Kenneth D. Whitney, Alan K. Knapp

Biological, Geological, and Environmental Faculty Publications

1. Plant traits can provide unique insights into plant performance at the community scale. Functional composition, defined by both functional diversity and community-weighted trait means (CWMs), can affect the stability of above-ground net primary production (ANPP) in response to climate extremes. Further complexity arises, however, when functional composition itself responds to environmental change. The duration of climate extremes, such as drought, is expected to increase with rising global temperatures; thus, understanding the impacts of long-term drought on functional composition and the corresponding effect that has on ecosystem function could improve predictions of ecosystem sensitivity to climate change.

2. We experimentally …

A Non-Natural Nucleotide Uses A Specific Pocket To Selectively Inhibit Telomerase Activity, Wilnelly Hernandez-Sanchez, Wei Huang, Brian Plucinsky, Nelson Garcia-Vazquez, Nathaniel J. Robinson, William P. Schiemann, Anthony J. Berdis, Emmanuel Skordalakes, Derek J. Taylor

Chemistry Faculty Publications

Telomerase, a unique reverse transcriptase that specifically extends the ends of linear chromosomes, is up-regulated in the vast majority of cancer cells. Here, we show that an indole nucleotide analog, 5-methylcarboxyl-indolyl-2′-deoxyriboside 5′-triphosphate (5-MeCITP), functions as an inhibitor of telomerase activity. The crystal structure of 5-MeCITP bound to the Tribolium castaneum telomerase reverse transcriptase reveals an atypical interaction, in which the nucleobase is flipped in the active site. In this orientation, the methoxy group of 5-MeCITP extends out of the canonical active site to interact with a telomerase-specific hydrophobic pocket formed by motifs 1 and 2 in the fingers domain and …

Analysis Of Oxygen-18 Labeled Phosphate To Study Positional Isotope Experiments Using Lc-Qtof-Ms, Sujatha Chilakala, Iteen Cheng, Ireen Lee, Yan Xu

Chemistry Faculty Publications

A method is proposed in this paper for the determination of oxygen-18 labeled phosphate so that positional isotope experiments using sensitive and rapid liquid chromatography–QTOF–mass spectrometry (LC-QTOF-MS) experiments can be carried out. The positional isotope exchange technique is a useful tool in understanding the mechanisms and kinetics of many enzyme-catalyzed reactions. Detection of the positions and concentration of these exchanged isotopes is the key. Gas chromatography–mass spectrometry (GC-MS) and nuclear magnetic resonance imaging are commonly used analytical techniques for measurement of ¹⁸O/¹⁶O, ³¹P and ¹⁵N isotope enrichment. Since these techniques either require a time-consuming derivatization …

An Examination Of The Death Penalty, Alexandra N. Kremer

The Downtown Review

The death penalty, or capital punishment, is the use of execution through hanging, beheading, drowning, gas chambers, lethal injection, and electrocution among others in response to a crime. This has spurred much debate on whether it should be used for reasons such as ethics, revenge, economics, effectiveness as a deterrent, and constitutionality. Capital punishment has roots that date back to the 18^th century B.C., but, as of 2016, has been abolished in law or practice by more than two thirds of the world’s countries and several states within the United States. Here, the arguments for and against the death …

With-In Host Dynamics Of L. Monocytogenes And Thresholds For Distinct Infection Scenarios, Ashrafur Rahman, Daniel Munther, Aamir Fazil, Ben Smith, Jianhong Wu

Mathematics and Statistics Faculty Publications

The case fatality and illness rates associated with L. monocytogenes continue to pose a serious public health burden despite the significant efforts and control protocol administered by private and public sectors. Due to the advance in surveillance and improvement in detection methodology, the knowledge of sources, transmission routes, growth potential in food process units and storage, effect of pH and temperature are well understood. However, the with-in host growth and transmission mechanisms of L. monocytogenes, particularly within the human host, remain unclear, largely due to the limited access to scientific experimentation on the human population. In order to provide insight …

Manganese Oxide/Hemin-Functionalized Graphene As A Platform For Peroxynitrite Sensing, Haitham F. Kalil, Shaimaa Maher, Tiyash Bose, Mekki Bayachou

Chemistry Faculty Publications

Peroxynitrite (ONOO−, PON) is a powerful oxidizing agent generated in vivo by the diffusion-limited reaction of nitric oxide (NO) and superoxide (O₂˙⁻) radicals. Under oxidative stress, cumulated peroxynitrite levels are associated with chronic inflammatory disorders and other pathophysiological conditions. The accurate detection of peroxynitrite in biological systems is important, not only to understand the genesis and development of diseases, but also to explore and design potential therapeutics. Herein, a manganese oxide/hemin-modified graphene interface is explored as a platform for peroxynitrite amperometric detection. Hemin-functionalized reduced graphene oxide was further modified with manganese oxide nanoparticles to provide a …

Advancing Risk Assessment: Mechanistic Dose-Response Modelling Of Listeria Monocytogenes Infection In Human Populations, Ashrafur Rahman, Daniel Munther, Aamir Fazil, Ben Smith, Jianhong Wu

Mathematics and Statistics Faculty Publications

Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited. The utility of characterizing the effects of strain variation and individual/subgroup susceptibility on dose-response outcomes has motivated the search for new approaches beyond the popular use of the exponential dose-response model for listeriosis. While descriptive models can account for such variation, they have limited power to extrapolate beyond the details of particular outbreaks. By contrast, this study exhibits dose-response relationships from a mechanistic basis, quantifying key biological factors involved in pathogen-host dynamics. An …

N-Glycosylation In The Protease Domain Of Trypsin-Like Serine Proteases Mediates Calnexin-Assisted Protein Folding, Hao Wang, Shuo Li, Juejin Wang, Shenghan Chen, Xue-Long Sun, Qingyu Wu

Chemistry Faculty Publications

Trypsin-like serine proteases are essential in physiological processes. Studies have shown that N-glycans are important for serine protease expression and secretion, but the underlying mechanisms are poorly understood. Here, we report a common mechanism of N-glycosylation in the protease domains of corin, enteropeptidase and prothrombin in calnexin-mediated glycoprotein folding and extracellular expression. This mechanism, which is independent of calreticulin and operates in a domain-autonomous manner, involves two steps: direct calnexin binding to target proteins and subsequent calnexin binding to monoglucosylated N-glycans. Elimination of N-glycosylation sites in the protease domains of corin, enteropeptidase and prothrombin inhibits corin and enteropeptidase cell surface …

A Galactomannoglucan Derived From Agaricus Brasiliensis: Purification, Characterization And Macrophage Activation Via Mapk And Ikappab/Nfkappab Pathways, Yanqing Zhang, Danting Liu, Leilei Fang, Xiaotong Zhao, Aimin Zhou, Junbo Xie

Chemistry Faculty Publications

In this study, a novel galactomannoglucan named as TJ2 was isolated from Agaricus brasiliensis with microwave extraction, macroporous resin, ion exchange resin and high resolution gel chromatography. TJ2 is composed of glucose, mannose and galactose in the ratio 99.2:0.2:0.6. Infrared spectra (IR), methylation analysis and nuclear magnetic resonance spectra indicated that TJ2 mainly contained a b-(1?3) – linked glucopyranosyl backbone. Interestingly, TJ2 significantly promoted RAW264.7 cell proliferation, and was able to activate the cells to engulf E. coli. In addition, TJ2 induced the expression of Interleukin 1b (IL-1b), Interleukin 6 (IL-6), tumor necrosis factor a (TNF-a) and cyclooxygenase-2 (Cox-2) in …

Biomimetic Macromolecules For Macrophage Targeting And Modulation, Joshua Whited

ETD Archive

Carbohydrate recognition has come to the forefront of biological aiming to uncover the mechanisms of physiological and pathological processes. Cell surface glycans are involved in processes including cellular adhesion, cell signaling, and immune response. A new approach for profiling cell surface glycans has great potential for a wide range of biomedical applications. Lectins have been conventionally used to determine the structure and function of glycoproteins, however, their numbers are still restricted compared to the number of glycan structures. Boronic acid has proven a remarkable small molecule capable of binding diols in aqueous solution. This interaction indicates boronic acid derived molecules …

Quantitative Analysis Of Bleomycin In Rat Plasma By Lc-Ms/Ms, Huawen Li

ETD Archive

Bleomycin is the most commonly used compound in its group of antineoplastic drugs. It works on tumor cells by single and double stranded DNA cleavage after its activation, in which it blocks tumor cells’ DNA replication or transcription activities to inhibit tumor cells’ growth. Bleomycin sulfate (Blenoxane) is the most popular preparation used in clinical research, and contains Bleomycin fractions of A2 and B2, which causes difficulties in quantitative analysis. This work uses the metal chelating property of Bleomycin as an advantage to simplify and improve sensitivity of existing quantitative methods. Copper was spiked in excess to plasma samples, followed …

Computational Investigation Of Protein Assemblies, Sm Bargeen Alam Turzo

ETD Archive

Selective nitrosylation of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) at Cys-247 affects gene regulation through the interferon-gamma (IFN- γ) activated inhibitor of translation (GAIT) complex. Oxidized low-density lipoprotein (LDL_ox) and INF-γ induce assembly of the nitrosylase complex composed of inducible nitric oxide synthase (iNOS), S100A8, and S100A9 proteins. Crystal structure of the complex of GAPDH and S100A8A9 is not known, structural prediction method were employed by protein-protein docking and binding energy calculation with PatchDock and FIREDock respectively. Candidate models were selected, based on a weight factor calculated, from the computational method developed from the "artificial protease" cleavage mapping Fe(III) (s)-1-(p- …

Il-17 Drives Copper Uptake And Activation Of Growth Pathways In Colorectal Cancer Cells In A Steap4-Dependent Manner, Evan Martin

ETD Archive

Colorectal cancer is a disease characterized by abnormal, invasive cell growth beginning in the colon or rectum. The third most common type of cancer worldwide, approximately one million new cases of the disease are diagnosed across the globe annually, resulting in an estimated 700,000+ deaths. One major risk factor associated with development of colorectal cancer is the presence of chronic inflammation in the large intestine, also known as colitis. Inflammation is a complex immune response against harmful stimuli, characterized by symptoms including heat, redness, swelling and pain. One important molecular mediator of this process is interleukin 17 (IL-17), a pro-inflammatory …

Il-17 Drives Copper Uptake And Activation Of Growth Pathways In Colorectal Cancer Cells In A Steap4-Dependent Manner, Evan Martin

ETD Archive

Colorectal cancer is a disease characterized by abnormal, invasive cell growth beginning in the colon or rectum. The third most common type of cancer worldwide, approximately one million new cases of the disease are diagnosed across the globe annually, resulting in an estimated 700,000+ deaths. One major risk factor associated with development of colorectal cancer is the presence of chronic inflammation in the large intestine, also known as colitis. Inflammation is a complex immune response against harmful stimuli, characterized by symptoms including heat, redness, swelling and pain. One important molecular mediator of this process is interleukin 17 (IL-17), a pro-inflammatory …

Toward The Crystallization Of An Archaeal Dihydrorotase, Haley Newman, Ryan Godin

Undergraduate Research Posters 2018

Dihydroorotase catalyzes the conversion of N-carbamoyl-L-aspartate to Ldihydroorotate in the de novo biosynthesis of pyrimidines. M. jannaschii is an archaeon that thrives in extreme environments such as the hypothermal vents at the bottom of the oceans in which both temperature and pressure are extremely high. It can serve as a model organism for research purposes. This experiment is a first step toward elucidating the structure of this enzyme in M. jannaschii. Our summer research started using a partially purified enzyme preparation from previous experiments. We further purified the enzyme primarily using hydrophobic interaction and hydroxyapatite chromatographies. Twenty-four closely related conditions …

Hybrid Extended Kalman Filtering And Noise Statistics Optimization For Produce Wash State Estimation, Vahid Azimi, Daniel Munther, Seyed Abolfazl Fakoorian, Thang Tien Nguyen, Daniel J. Simon

Mathematics and Statistics Faculty Publications

Food-borne diseases associated with fresh produce consistently cause serious public health issues. Although sanitization measures are utilized to enhance the safety of fresh produce, strategies that neglect the dynamic nature of commercial wash processes are limited, creating the potential for pathogen cross-contamination and major disease outbreaks. In light of this risk, there is an urgent need for new control approaches during produce washing to reduce the probability of outbreaks. As an important step in this direction, a hybrid extended Kalman filter (HEKF) and particle swarm optimization (PSO)-based noise statistics optimization are designed for a produce wash system. The HEKF uses …

The Future Perspective: Metabolomics In Laboratory Medicine For Inborn Errors Of Metabolism, Yana Sandlers

Chemistry Faculty Publications

Metabolomics can be described as a simultaneous and comprehensive analysis of small molecules in a biological sample. Recent technological and bioinformatics advances have facilitated large-scale metabolomic studies in many areas, including inborn errors of metabolism (IEMs). Despite significant improvements in the diagnosis and treatment of some IEMs, it is still challenging to understand how genetic variation affects disease progression and susceptibility. In addition, a search for new more personalized therapies and a growing demand for tools to monitor the long-term metabolic effects of existing therapies set the stage for metabolomics integration in preclinical and clinical studies. While targeted metabolomics approach …

Development And Validation Of A Novel Lc–Ms/Ms Method For Simultaneous Determination Of Abiraterone And Its Seven Steroidal Metabolites In Human Serum: Innovation In Separation Of Diastereoisomers Without Use Of A Chiral Column, Mohammad Alyamani, Zhenfei Li, Sunil K. Upadhyay, David J. Anderson, Richard J. Auchus, Nima Sharifi

Chemistry Faculty Publications

Abiraterone acetate (AA), the prodrug of abiraterone, is FDA-approved for the treatment of castration-resistant prostate cancer. Abiraterone is metabolized in patients to a more potent analogue, D4A. However, we have recently reported that this analogue is further metabolized to additional metabolites in patients treated with AA. Here, we present a liquid chromatography-tandem mass spectrometry method developed to resolve and detect abiraterone and its seven metabolites in human serum using an AB Sciex Qtrap 5500 mass analyzer coupled with a Shimadzu Nexera UPLC station. Analytes and the internal standard (abiraterone-d4) were extracted from human serum using the liquid–liquid extraction procedure. The …

Inhibiting Translesion Dna Synthesis As An Approach To Combat Drug Resistance To Dna Damaging Agents, Jung-Suk Choi, Seol Kim, Edward Motea, Anthony J. Berdis

Chemistry Faculty Publications

Anti-cancer agents exert therapeutic effects by damaging DNA. Unfortunately, DNA polymerases can effectively replicate the formed DNA lesions to cause drug resistance and create more aggressive cancers. To understand this process at the cellular level, we developed an artificial nucleoside that visualizes the replication of damaged DNA to identify cells that acquire drug resistance through this mechanism. Visualization is achieved using "click" chemistry to covalently attach azide-containing fluorophores to the ethynyl group present on the nucleoside analog after its incorporation opposite damaged DNA. Flow cytometry and microscopy techniques demonstrate that the extent of nucleotide incorporation into genomic DNA is enhanced …

Unreplicable: The Unscientific Nature Of Science Journals, Ernest M. Oleksy

The Downtown Review

Academia shapes the way our species looks at veracity and defines what is deemed as well-founded science. The platform for researchers to make their work known is academic journals. The prerogative of these journals is to disseminate technically sound work so that the public may be informed of up-to-date advances in scientific fields. However, these journals are products on the market whose ultimate purpose is to garner a following that will make the producers money. This results in research that does not have statistically significant findings, or replications of past experiments which are integral to supporting the findings of the …

Hmba Is A Putative Hsp70 Activator Stimulating Hexim1 Expression That Is Down-Regulated By Estrogen, Rati Lama, Chunfang Gan, Nethrie Idippily, Viharika Bobba, David Danielpour, Monica Montano, Bin Su Ph.D.

Chemistry Faculty Publications

Hexamethylene bis-acetamide inducible protein 1 (HEXIM1) is identified as a novel inhibitor of estrogen stimulated breast cell growth, and it suppresses estrogen receptor-a transcriptional activity. HEXIM1 protein level has been found to be downregulated by estrogens. Recently, HEXIM1 has been found to inhibit androgen receptor transcriptional activity as well. Researchers have used Hexamethylene bisacetamide (HMBA) for decades to stimulate HEXIM1 expression, which also inhibit estrogen stimulated breast cancer cell gene activation and androgen stimulated prostate cancer gene activation. However, the direct molecular targets of HMBA that modulate the induction of HEXIM1 expression in mammalian cells have not been identified. Based …