Comparison Of Human Cytokine Array, Cytokine Bead Arrays, And Protein Elisa In Determining Cytokine Production In Media Supernatant From In Vitro Strain Of Human Dermal Fibroblasts, 2019 Marian University - Indianapolis
Comparison Of Human Cytokine Array, Cytokine Bead Arrays, And Protein Elisa In Determining Cytokine Production In Media Supernatant From In Vitro Strain Of Human Dermal Fibroblasts, Aric Anloague, Jonathan W. Lowery Ph.D.
Student Publications and Research
This experiment analyzes three different techniques used in literature to detect cytokine release from cells in vitro: the Human Cytokine Array (HCA) by R&D Systems, the BD Cytometric Bead Array (CBA) assay, and protein enzyme-linked immunosorbent assay (ELISA). The model used to test these assays was a human dermal fibroblast cell culture that was subjected to strain profiles by the Flexcell FX-6000 that include a repetitive motion injury, a profile with the injury strain as well as a strain representing myofascial release, and a control that was not strained. Each of these techniques analyzed the conditioned media of the ...
Cc Chemokine Ccl1 Receptor Ccr8 Mediates Conversion Of Mesenchymal Stem Cells To Embryoid Bodies Expressing Foxp3+Ccr8+ Regulatory T Cells, Nasreen Haque, Niloufar Haque, Tuteja Akaash
Publications and Research
Embryoid bodies (EBs) are three dimensional aggregates of pluripotent stem cells primarily used to investigate morphogenesis and cell toxicity, are also attractive tools in regenerative medicine. While embryonic stem cells (ESCs) and induced pluripotent cells (IPSCs) have been shown to form EBs in mouse, primate and humans, EB formation have not been previously demonstrated in mesenchymal stem cells (MSCs). Here we show that rat MSCs form EBs; which express regulatory T cell (Treg) marker Foxp3 and CC chemokine CCL1 receptor CCR8. We show a novel method for formation of EBs from MSCs under stress and demonstrate that the induction of ...
Systems Approach Reveals Photosensitivity And Per2 Level As Determinants Of Clock-Modulator Efficacy, 2019 Korea Advanced Institute of Science and Technology
Systems Approach Reveals Photosensitivity And Per2 Level As Determinants Of Clock-Modulator Efficacy, Dae Wook Kim, Cheng Chang, Xian Chen, Angela C. Doran, Francois Gaudreault, Travis Wager, George J. Demarco, Jae Kyoung Kim
Open Access Articles
In mammals, the master circadian clock synchronizes daily rhythms of physiology and behavior with the day-night cycle. Failure of synchrony, which increases the risk for numerous chronic diseases, can be treated by phase adjustment of the circadian clock pharmacologically, for example, with melatonin, or a CK1delta/epsilon inhibitor. Here, using in silico experiments with a systems pharmacology model describing molecular interactions, and pharmacokinetic and behavioral experiments in cynomolgus monkeys, we find that the circadian phase delay caused by CK1delta/epsilon inhibition is more strongly attenuated by light in diurnal monkeys and humans than in nocturnal mice, which are common preclinical ...
Dysfunction In Serotonergic And Noradrenergic Systems And Somatic Symptoms In Psychiatric Disorders, 2019 The Second Xiangya Hospital of Central South University
Dysfunction In Serotonergic And Noradrenergic Systems And Somatic Symptoms In Psychiatric Disorders, Yi Liu, Jingping Zhao, Xiaoduo Fan, Wenbin Guo
Open Access Articles
Somatic symptoms include a range of physical experiences, such as pain, muscle tension, body shaking, difficulty in breathing, heart palpitation, blushing, fatigue, and sweating. Somatic symptoms are common in major depressive disorder (MDD), anxiety disorders, and some other psychiatric disorders. However, the etiology of somatic symptoms remains unclear. Somatic symptoms could be a response to emotional distress in patients with those psychiatric conditions. Increasing evidence supports the role of aberrant serotoninergic and noradrenergic neurotransmission in somatic symptoms. The physiological alterations underlying diminished serotonin (5-HT) and norepinephrine (NE) signaling may contribute to impaired signal transduction, reduced 5-HT, or NE release from ...
Supervised Dimension Reduction For Large-Scale "Omics" Data With Censored Survival Outcomes Under Possible Non-Proportional Hazards, Lauren Spirko-Burns, Karthik Devarajan
COBRA Preprint Series
The past two decades have witnessed significant advances in high-throughput ``omics" technologies such as genomics, proteomics, metabolomics, transcriptomics and radiomics. These technologies have enabled simultaneous measurement of the expression levels of tens of thousands of features from individual patient samples and have generated enormous amounts of data that require analysis and interpretation. One specific area of interest has been in studying the relationship between these features and patient outcomes, such as overall and recurrence-free survival, with the goal of developing a predictive ``omics" profile. Large-scale studies often suffer from the presence of a large fraction of censored observations and potential ...
A Human Papillomavirus-Independent Cervical Cancer Animal Model Reveals Unconventional Mechanisms Of Cervical Carcinogenesis, 2019 Massachusetts General Hospital & University of Nebraska Medical Center & Huazhong Agricultural University
A Human Papillomavirus-Independent Cervical Cancer Animal Model Reveals Unconventional Mechanisms Of Cervical Carcinogenesis, Chunbo He, Xiangmin Lv, Cong Huang, Peter C. Angeletti, Guohua Hua, Jixin Dong, Jin Zhou, Zhengfeng Wang, Bowen Ma, Xingcheng Chen, Paul F. Lambert, Bo R. Rueda, John S. Davis, Cheng Wang
HPV infections are common in healthy women and only rarely cause cervical cancer, suggesting that individual genetic susceptibility may play a critical role in the establishment of persistent HPV infection and the development of cervical cancer. Here, we provide convincing in vitro and in vivo evidence showing that differential expression and activation of YAP1 oncogene determine individual susceptibility to HPV infection and cervical carcinogenesis. We found that hyperactivation of YAP1 in mouse cervical epithelium was sufficient to induce invasive cervical cancer. Cervical epithelial cell-specific HPV16 E6/E7 and YAP1 double-knockin mouse model demonstrated that high-risk HPV synergized with hyperactivated YAP1 ...
An Investigation Of Stimulants: Reviewing Their Effects On The Brain, Including Memory And Microglia, 2019 University of Nebraska at Omaha
An Investigation Of Stimulants: Reviewing Their Effects On The Brain, Including Memory And Microglia, Michael Douchey
Student Research and Creative Activity Fair
Stimulants are a class of drugs that have a variety of effects on the brain, including changes in receptor activity in the brain areas responsible for- memory, attention, emotion, motor control, and the reward pathway. Stimulants may be generally classified by their availability. For example, prescription stimulants, which include drugs such as methylphenidate (Concerta™, Ritalin™) and mixed amphetamine salts (Adderall™), must be prescribed by medical professionals. Another regulated stimulant, albeit one available without a prescription, is nicotine; a highly addictive chemical that is age-restricted by the U.S. federal government. Nicotine is found in tobacco products, and in tobacco-free alternatives ...
Large Scale Dynamical Model Of Macrophage/Hiv Interactions, 2019 University of Nebraska at Omaha
Large Scale Dynamical Model Of Macrophage/Hiv Interactions, Sean T. Bresnahan, Matthew M. Froid
Student Research and Creative Activity Fair
Properties emerge from the dynamics of large-scale molecular networks that are not discernible at the individual gene or protein level. Mathematical models - such as probabilistic Boolean networks - of molecular systems offer a deeper insight into how these emergent properties arise. Here, we introduce a non-linear, deterministic Boolean model of protein, gene, and chemical interactions in human macrophage cells during HIV infection. Our model is composed of 713 nodes with 1583 interactions between nodes and is responsive to 38 different inputs including signaling molecules, bacteria, viruses, and HIV viral particles. Additionally, the model accurately simulates the dynamics of over 50 different ...
Cyclin D1 Integrates G9a-Mediated Histone Methylation., 2019 Baruch S. Blumberg Institute
Cyclin D1 Integrates G9a-Mediated Histone Methylation., Zhiping Li, Xuanmao Jiao, Gabriele Di Sante, Adam Ertel, Mathew C. Casimiro, Min Wang, Sanjay Katiyar, Xiaoming Ju, D. V. Klopfenstein, Aydin Tozeren, William Dampier, Iouri Chepelev, Albert Jeltsch, Richard G. Pestell
Department of Cancer Biology Faculty Papers
Lysine methylation of histones and non-histone substrates by the SET domain containing protein lysine methyltransferase (KMT) G9a/EHMT2 governs transcription contributing to apoptosis, aberrant cell growth, and pluripotency. The positioning of chromosomes within the nuclear three-dimensional space involves interactions between nuclear lamina (NL) and the lamina-associated domains (LAD). Contact of individual LADs with the NL are dependent upon H3K9me2 introduced by G9a. The mechanisms governing the recruitment of G9a to distinct subcellular sites, into chromatin or to LAD, is not known. The cyclin D1 gene product encodes the regulatory subunit of the holoenzyme that phosphorylates pRB and NRF1 thereby governing ...
Persistent Viral Reservoirs In Lymphoid Tissues In Siv-Infected Rhesus Macaques Of Chinese-Origin On Suppressive Antiretroviral Therapy, 2019 Tulane National Primate Research Center
Persistent Viral Reservoirs In Lymphoid Tissues In Siv-Infected Rhesus Macaques Of Chinese-Origin On Suppressive Antiretroviral Therapy, Summer Siddiqui, Stefanie Perez, Yong Gao, Lara Doyle-Meyers, Brian T. Foley, Qingsheng Li, Binhua Ling
Understanding HIV latent reservoirs in tissues is essential for the development of new strategies targeting these sites for eradication. Here, we assessed the size of latent reservoirs and the source of residual viruses in multiple lymphoid tissues of SIV-infected and fully suppressed rhesus macaques of Chinese-origin (cRMs). Eight cRMs were infected with SIVmac251 and treated with tenofovir and emtricitabine daily for 24 weeks initiated 4 weeks post-infection. Four of the eight animals reached sustained full viral suppression with undetectable viremia. The levels of cell-associated SIV DNA varied in peripheral blood mononuclear cells (PBMCs) and multiple lymphoid tissues, but with higher ...
Relationship Between The Cervical Microbiome, Hiv Status, And Precancerous Lesions, 2019 University of Nebraska - Lincoln
Relationship Between The Cervical Microbiome, Hiv Status, And Precancerous Lesions, Cameron Klein, Daniela Gonzalez, Kandali Samwel, Crispin Kahesa, Julius Mwaiselage, Nirosh Aluthge, Samodha Fernando, John T. West, Charles Wood, Peter C. Angeletti
Nearly all cervical cancers are causally associated with human papillomavirus (HPV). The burden of HPV-associated dysplasias in sub-Saharan Africa is influenced by HIV. To investigate the role of the bacterial microbiome in cervical dysplasia, cytobrush samples were collected directly from cervical lesions of 144 Tanzanian women. The V4 hypervariable region of the 16S rRNA gene was amplified and deep sequenced. Alpha diversity metrics (Chao1, PD whole tree, and operational taxonomic unit [OTU] estimates) displayed significantly higher bacterial richness in HIV-positive patients (P = 0.01) than in HIV-negative patients. In HIV-positive patients, there was higher bacterial richness in patients with high-grade ...
Salmonella Within Macrophages--An Extreme Host-Pathogen Interface: Small Molecule Inhibitors Of Bacterial Efflux And The Roles Of Bacterial Lipid Metabolism And Mammalian Co-Culture During Infection, 2019 University of Colorado at Boulder
Salmonella Within Macrophages--An Extreme Host-Pathogen Interface: Small Molecule Inhibitors Of Bacterial Efflux And The Roles Of Bacterial Lipid Metabolism And Mammalian Co-Culture During Infection, Abigail L. Reens
Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations
Pathogens withstand extreme host environments during infection. Salmonella enterica serovar Typhimurium survives within host macrophages, immune cells intended to phagocytose and destroy pathogens. Through decades of study, we know much about how Salmonella endures this challenging niche. I leveraged this host-pathogen interface to identify small molecules that disrupt Salmonella infection of macrophages. I developed a medium-throughput fluorescence microscopy-based screening assay and image analysis pipeline to quantify intracellular bacterial load. With this platform, I identified 300 small molecules that reduce Salmonella infection of macrophages. Of the top 60 hits, I characterized three compounds that inhibit bacterial efflux pumps and sensitize Salmonella ...
Characterization Of The Novel Interaction Between Neisseria Gonorrhoeae Tdfj And Its Human Ligand S100a7, 2019 Virginia Commonwealth University
Characterization Of The Novel Interaction Between Neisseria Gonorrhoeae Tdfj And Its Human Ligand S100a7, Stavros Maurakis
Theses and Dissertations
Neisseria gonorrhoeae is an obligate human pathogen that causes the common STI gonorrhea, which presents a growing threat to global health. The WHO estimated 78 million new cases of gonorrhea worldwide in 2017, with estimates of 820,000 new cases in the United States alone according to the CDC. High-frequency phase and antigenic variation inherent in N. gonorrhoeae, coupled with its natural ability to rapidly acquire and stably integrate antimicrobial resistance factors into its genome, have culminated in an infection against which there is no effective vaccine, and for which the list of viable therapeutic options is quickly shrinking. Moreover ...
Caspases And Cancer: Connections Through Circular Dichroism Spectroscopy, 2019 Georgia Southern University
Caspases And Cancer: Connections Through Circular Dichroism Spectroscopy, Sarah M. Hethcox
University Honors Program Theses
While excessive cell death inevitably leads to negative effects, the endurance of damaged cells in the presence of death signals can be equally detrimental to health. Apoptosis, or programmed cell death, is a highly regulated process in which cues from within or from outside a cell can trigger an irreversible sequence of signals that carry out cell destruction known as the apoptotic cascade. A group of enzymes called caspases play a vital role in this cascade with some participating as initiators and others acting as effectors of protein cleavage and intracellular breakdown. Although it is normal for the activity of ...
Agent Based Model Of Cavitation In Spinal Cord Injury, 2019 Bard College
Agent Based Model Of Cavitation In Spinal Cord Injury, Rahma Ahmed
Senior Projects Spring 2019
Annually, approximately 375,000 people suffer from spinal cord injury (SCI) worldwide and many SCI patients develop secondary health conditions such as respiratory, cardiovascular, and urinary/bowel complications which negatively impact their daily lives. SCI occurs when there is damage to the spinal cord resulting in decreased motor functions, decreased sensory functions, or paralysis. Days to weeks after initial impact, the lesion (area of injury) continues to increase in size in a process called progressive cavitation which demyelinates axons and inhibits effective axonal regeneration. In an in vitro model of progressive cavitation, Fitch et al. showed that activated macrophages cause ...
Regulation Of Na-K-Atpase By Arachidonic Acid Metabolites In Intestinal Epithelial Cells, 2019 Marshall University
Regulation Of Na-K-Atpase By Arachidonic Acid Metabolites In Intestinal Epithelial Cells, Niraj Nepa
Theses, Dissertations and Capstones
The integral membrane protein sodium potassium adenosine triphosphate (Na-K-ATPase), has been extensively studied in various animal cell models. Na-K-ATPase is a multifunctional enzyme which plays a significant role in cellular physiology by regulating electrochemical potential, cell volume, pH, cytosolic calcium, and many nutrient and electrolyte transport processes. As such, it has been implicated in the pathogenesis of inflammatory bowel diseases (IBD) and has been shown to play a vital role in the malabsorption of nutrients and electrolytes. In this context, a significant amount of research has been done over the last two decades to understand the mechanisms of alteration of ...
A Single-Cycle Adenovirus Type 7 Vaccine For Prevention Of Acute Respiratory Disease, 2019 University of Nebraska - Lincoln
A Single-Cycle Adenovirus Type 7 Vaccine For Prevention Of Acute Respiratory Disease, Brianna L. Bullard, Brigette N. Corder, Eric A. Weaver
Adenovirus type 7 (Ad7) infection is associated with acute respiratory disease (ARD), especially in military recruits living in close quarters. Recently, several outbreaks of Ad7 infections have occurred in civilian populations, with some cases leading to death. However, the current Ad7 vaccine is licensed for use only in military recruits because it utilizes an orally delivered wild type virus which is shed in the stool for 28 days after immunization. This poses a safety risk due to the possibility of virus spread to vulnerable populations. To address the need for a safer Ad7 vaccine for use in civilian populations, we ...
A Poxvirus Pseudokinase Represses Viral Dna Replication Via A Pathway Antagonized By Its Paralog Kinase, 2019 University of Nebraska - Lincoln
A Poxvirus Pseudokinase Represses Viral Dna Replication Via A Pathway Antagonized By Its Paralog Kinase, Annabel T. Olson, Zhigang Wang, Amber B. Rico, Matthew S. Wiebe
Poxviruses employ sophisticated, but incompletely understood, signaling pathways that engage cellular defense mechanisms and simultaneously ensure viral factors are modulated properly. For example, the vaccinia B1 protein kinase plays a vital role in inactivating the cellular antiviral factor BAF, and likely orchestrates other pathways as well. In this study, we utilized experimental evolution of a B1 deletion virus to perform an unbiased search for suppressor mutations and identify novel pathways involving B1. After several passages of the ΔB1 virus we observed a robust increase in viral titer of the adapted virus. Interestingly, our characterization of the adapted viruses reveals that ...
Near-Atomic Structure Of A Giant Virus, 2019 Purdue University
Near-Atomic Structure Of A Giant Virus, Qianglin Fang, Dongjie Zhu, Irina Agarkova, Jagat Adhikari, Thomas Klose, Yue Liu, Zhenguo Chen, Yingyuan Sun, Michael L. Gross, James L. Van Etten, Xinzheng Zhang, Michael G. Rossmann
Although the nucleocytoplasmic large DNA viruses (NCLDVs) are one of the largest group of viruses that infect many eukaryotic hosts, the near-atomic resolution structures of these viruses have remained unknown. Here we describe a 3.5 Å resolution icosahedrally averaged capsid structure of Paramecium bursaria chlorella virus 1 (PBCV-1). This structure consists of 5040 copies of the major capsid protein, 60 copies of the penton protein and 1800 minor capsid proteins of which there are 13 different types. The minor capsid proteins form a hexagonal network below the outer capsid shell, stabilizing the capsid by binding neighboring capsomers together. The ...
Exosomes And Their Complex Role In Pathogenesis, 2019 Iowa State University
Exosomes And Their Complex Role In Pathogenesis, William Young
No abstract provided.