A Compromised Liver Alters Polychlorinated Biphenyl-Mediated Toxicity,
2017
University of Kentucky
A Compromised Liver Alters Polychlorinated Biphenyl-Mediated Toxicity, Banrida Wahlang, Jordan T. Perkins, Michael C. Petriello, Jessie B. Hoffman, Arnold J. Stromberg, Bernhard Hennig
Superfund Research Center Faculty Publications
Exposure to environmental toxicants namely polychlorinated biphenyls (PCBs) is correlated with multiple health disorders including liver and cardiovascular diseases. The liver is important for both xenobiotic and endobiotic metabolism. However, the responses of an injured liver to subsequent environmental insults has not been investigated. The current study aims to evaluate the role of a compromised liver in PCB-induced toxicity and define the implications on overall body homeostasis. Male C57Bl/6 mice were fed either an amino acid control diet (CD) or a methionine-choline deficient diet (MCD) during the 12-week study. Mice were subsequently exposed to either PCB126 (4.9 mg/kg) or the …
Effects Of Binding Affinity Between Bovine Serum Albumin And Platinum Drugs,
2017
Western Kentucky University
Effects Of Binding Affinity Between Bovine Serum Albumin And Platinum Drugs, Nathan Puckett
Masters Theses & Specialist Projects
Platinum complex drugs such as cisplatin have been used as highly successful chemotherapy drugs since the 1970s. We are interested in how the ligands attached to cisplatin analogs influences their reactivity with biologically relevant targets along with time and amount. For this study, reactions were conducted to determine the reactivity between different platinum compounds and the protein bovine serum albumin. Various platinum compounds with different ligands were reacted in varying amounts with albumin in ammonium acetate buffer for either 1 hour, 4 hours, or 24 hours. Each reaction was quenched after the designated reaction time by dialysis and the platinum …
The Methane-Oxidizing Capability Of Pumice Biocovers On Icelandic Landfills,
2017
SIT Study Abroad
The Methane-Oxidizing Capability Of Pumice Biocovers On Icelandic Landfills, Mitchell P. Miller
Independent Study Project (ISP) Collection
Pumice has been shown in laboratory biofilter experiments to improve the oxidation of methane (Pratt et al. 2012, Pratt, Tate, & Deslippe 2012). Pumice biocovers were tested on two Icelandic landfills, Kirkjuferjuhjáleiga and Álfsnes. Seven biocover plots were dug and filled with a 50:50 blend of pumice and native soil. CH4 and CO2 were measured using the static chamber method before and after biocover placement. After one week, the CH4:CO2 ratio was reduced on four of the seven plots, weakly indicating that pumice biocovers may be an effective way to better oxidize landfill methane.
Factors That Determine Civil Action In Opposition To Hydroelectric Development Along The Chiriquí Viejo River In The Chiriquí Province Of Panamá,
2017
SIT Study Abroad
Factors That Determine Civil Action In Opposition To Hydroelectric Development Along The Chiriquí Viejo River In The Chiriquí Province Of Panamá, Nora Sawyer
Independent Study Project (ISP) Collection
Hydroelectric development has increased rapidly throughout Latin America in the late 20th and early 21st centuries (del Mar Rubio et al. 2014). In 2014, Latin America represented 20 percent of the world’s hydropower (del Mar Rubio et al. 2014). It is also the main source of power generation throughout Latin America, accounting for roughly 65 percent of all electricity generated (Wheeler 2012). Within Panamá, significant hydroelectric development has been happening in the Chiriquí province. Local peoples’ dissatisfaction with the actions of the hydropower companies has increased with time, resulting in civilians and organizations taking action in opposition to these companies …
Biokinetics Of Nanomaterials: The Role Of Biopersistence,
2017
German Federal Institute for Risk Assessment, Germany
Biokinetics Of Nanomaterials: The Role Of Biopersistence, Peter Laux, Christian Riebeling, Andy M. Booth, Joseph D. Brain, Josephine Brunner, Cristina Cerrillo, Otto Creutzenberg, Irina Estrela-Lopis, Thomas Gebel, Gunnar Johanson, Harald Jungnickel, Heiko Kock, Jutta Tentschert, Ahmed Tlili, Andreas Schäffer, Adriënne J. A. M. Sips, Robert A. Yokel, Andreas Luch
Pharmaceutical Sciences Faculty Publications
Nanotechnology risk management strategies and environmental regulations continue to rely on hazard and exposure assessment protocols developed for bulk materials, including larger size particles, while commercial application of nanomaterials (NMs) increases. In order to support and corroborate risk assessment of NMs for workers, consumers, and the environment it is crucial to establish the impact of biopersistence of NMs at realistic doses. In the future, such data will allow a more refined categorization of NMs. Despite many experiments on NM characterization and numerous in vitro and in vivo studies, several questions remain unanswered including the influence of biopersistence on the toxicity …
Thiamine Deficiency Induces Endoplasmic Reticulum Stress And Oxidative Stress In Human Neurons Derived From Induced Pluripotent Stem Cells,
2017
University of Kentucky
Thiamine Deficiency Induces Endoplasmic Reticulum Stress And Oxidative Stress In Human Neurons Derived From Induced Pluripotent Stem Cells, Xin Wang, Mei Xu, Jacqueline A. Frank, Zun-Ji Ke, Jia Luo
Pharmacology and Nutritional Sciences Faculty Publications
Thiamine (vitamin B1) deficiency (TD) plays a major role in the etiology of Wernicke's encephalopathy (WE) which is a severe neurological disorder. TD induces selective neuronal cell death, neuroinflammation, endoplasmic reticulum (ER) stress and oxidative stress in the brain which are commonly observed in many aging-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and progressive supranuclear palsy (PSP). However, the underlying cellular and molecular mechanisms remain unclear. The progress in this line of research is hindered due to the lack of appropriate in vitro models. The neurons derived for the human induced pluripotent stem …
Investigation De Regeneración Natural De Plantas Vasculares En La Reserva Madrigal Del Podocarpus / Investigation Of Natural Regeneration Of Vascular Plants In The Madrigal Reserve Of The Podocarpus,
2017
SIT Study Abroad
Investigation De Regeneración Natural De Plantas Vasculares En La Reserva Madrigal Del Podocarpus / Investigation Of Natural Regeneration Of Vascular Plants In The Madrigal Reserve Of The Podocarpus, Sy Baker
Independent Study Project (ISP) Collection
En el Sur de Ecuador, hay una historia larga de incendio que está asociada con la historia de la agricultura y ganadería a causa de las técnicas de tala y quema para despejar áreas para campos y también quemaduras intencionales para fertilizar los suelos y mejorar productividad agrícola (Fernandez et al 2015). En los últimos días de Noviembre de 2016, un incendio quemó campos, la Reserva Madrigal de Podocarpus, y parte del Parque Nacional Podocarpus en Loja, Ecuador—el enfoque de este estudio. En este estudio: (1) se registraron las especies y distribución de plantas pioneras y sobrevivientes, (2) la se …
Enzyme-Dependent Fluorescence Recovery Of Nadh After Photobleaching To Assess Dehydrogenase Activity Of Isolated Perfused Hearts.,
2017
George Washington University
Enzyme-Dependent Fluorescence Recovery Of Nadh After Photobleaching To Assess Dehydrogenase Activity Of Isolated Perfused Hearts., Angel Moreno, Sarah Kuzmiak-Glancy, Rafael Jaimes, Matthew W Kay
Pharmacology and Physiology Faculty Publications
Reduction of NAD(+) by dehydrogenase enzymes to form NADH is a key component of cellular metabolism. In cellular preparations and isolated mitochondria suspensions, enzyme-dependent fluorescence recovery after photobleaching (ED-FRAP) of NADH has been shown to be an effective approach for measuring the rate of NADH production to assess dehydrogenase enzyme activity. Our objective was to demonstrate how dehydrogenase activity could be assessed within the myocardium of perfused hearts using NADH ED-FRAP. This was accomplished using a combination of high intensity UV pulses to photobleach epicardial NADH. Replenishment of epicardial NADH fluorescence was then imaged using low intensity UV illumination. NADH …
Proteome Dynamics During Postnatal Mouse Corpus Callosum Development.,
2017
George Washington University
Proteome Dynamics During Postnatal Mouse Corpus Callosum Development., Alexander I Son, Xiaoqin Fu, Fumikazu Suto, Judy S Liu, Kazue Hashimoto-Torii, Masaaki Torii
Pharmacology and Physiology Faculty Publications
Formation of cortical connections requires the precise coordination of numerous discrete phases. This is particularly significant with regard to the corpus callosum, whose development undergoes several dynamic stages including the crossing of axon projections, elimination of exuberant projections, and myelination of established tracts. To comprehensively characterize the molecular events in this dynamic process, we set to determine the distinct temporal expression of proteins regulating the formation of the corpus callosum and their respective developmental functions. Mass spectrometry-based proteomic profiling was performed on early postnatal mouse corpus callosi, for which limited evidence has been obtained previously, using stable isotope of labeled …
Role Of Cytokines And Chemokines In Alcohol-Induced Tumor Promotion,
2017
Anhui Medical University, China
Role Of Cytokines And Chemokines In Alcohol-Induced Tumor Promotion, Danlei Chen, Fengyun Zhang, Haifeng Ren, Jia Luo, Siying Wang
Pharmacology and Nutritional Sciences Faculty Publications
Excessive chronic alcohol consumption has become a worldwide health problem. The oncogenic effect of chronic alcohol consumption is one of the leading concerns. The mechanisms of alcohol-induced tumorigenesis and tumor progression are largely unknown, although many factors have been implicated in the process. This review discusses the recent progress in this research area with concentration on alcohol-induced dysregulation of cytokines and chemokines. Based on the available evidence, we propose that alcohol promotes tumor progression by the dysregulation of the cytokine/chemokine system. In addition, we discuss specific transcription factors and signaling pathways that are involved in the action of these cytokines/chemokines …
A Role Of Central Nell2 In The Regulation Of Feeding Behavior In Rats.,
2017
George Washington University
A Role Of Central Nell2 In The Regulation Of Feeding Behavior In Rats., Jin Kwon Jeong, Jae Geun Kim, Han Rae Kim, Tae Hwan Lee, Jeong Woo Park, Byung Ju Lee
Pharmacology and Physiology Faculty Publications
A brain-enriched secreting signal peptide, NELL2, has been suggested to play multiple roles in the development, survival, and activity of neurons in mammal. We investigated here a possible involvement of central NELL2 in regulating feeding behavior and metabolism. In situ hybridization and an immunohistochemical approach were used to determine expression of NELL2 as well as its colocalization with proopiomelanocortin (POMC) and neuropeptide Y (NPY) in the rat hypothalamus. To investigate the effect of NELL2 on feeding behavior, 2 nmole of antisense NELL2 oligodeoxynucleotide was administered into the lateral ventricle of adult male rat brains for 6 consecutive days, and changes …
Mammary Epithelial Polarity And Macrophage Infiltration,
2017
University of Kentucky
Mammary Epithelial Polarity And Macrophage Infiltration, Ren Xu
Pharmacology and Nutritional Sciences Faculty Publications
Loss of epithelial cell polarity and inflammation are hallmarks of breast cancer development. Although the association between the disruption of tissue polarity and inflammation has been demonstrated, we know little about how these two events are coupled. Using the 3D co-culture model of mammary epithelial cells and monocytes, a recent study reveals a link between disruption of epithelial polarity and monocytes infiltration.
Pulmonary Surfactant Fortified With Cath-2 As A Novel Therapy For Bacterial Pneumonia,
2017
University of Western Ontario
Pulmonary Surfactant Fortified With Cath-2 As A Novel Therapy For Bacterial Pneumonia, Brandon J. Baer
Western Research Forum
Background: Bacterial pneumonia is a leading cause of death worldwide, with high mortality rates persisting even after antibiotic treatment. Current treatments for pneumonia involve administration of antibiotics, however after the bacteria are killed they release toxic substances that induce inflammation and lung dysfunction. Host defense peptides represent a potential solution to this problem through their ability to down regulate inflammation. However, effective delivery to the lung is difficult because of the complex branching structure of the airways. My study addresses this delivery problem by using exogenous surfactant, a pulmonary delivery vehicle capable of improving spreading of these peptides throughout the …
Chemogenetic Stimulation Of The Hypoglossal Neurons Improves Upper Airway Patency,
2017
George Washington University
Chemogenetic Stimulation Of The Hypoglossal Neurons Improves Upper Airway Patency, Thomas Curado, Kenneth Fishbein, Huy Pho, Michael Brennick, Olga Dergacheva, David Mendelowitz, +Several Additional Authors
Pharmacology and Physiology Faculty Publications
Obstructive sleep apnea (OSA) is characterized by recurrent upper airway obstruction during sleep. OSA leads to high cardiovascular morbidity and mortality. The pathogenesis of OSA has been linked to a defect in neuromuscular control of the pharynx. There is no effective pharmacotherapy for OSA. The objective of this study was to determine whether upper airway patency can be improved using chemogenetic approach by deploying designer receptors exclusively activated by designer drug (DREADD) in the hypoglossal motorneurons. DREADD (rAAV5-hSyn-hM3(Gq)-mCherry) and control virus (rAAV5-hSyn-EGFP) were stereotactically administered to the hypoglossal nucleus of C57BL/6J mice. In 6–8 weeks genioglossus EMG and dynamic MRI …
Oxidative Stress-Driven Parvalbumin Interneuron Impairment As A Common Mechanism In Models Of Schizophrenia,
2017
George Washington University
Oxidative Stress-Driven Parvalbumin Interneuron Impairment As A Common Mechanism In Models Of Schizophrenia, P Steullet, J Cabungcal, J Coyle, M Didriksen, K Gill, Anthony-Samuel Lamantia, +Several Additional Authors
Pharmacology and Physiology Faculty Publications
Parvalbumin inhibitory interneurons (PVIs) are crucial for maintaining proper excitatory/inhibitory balance and high-frequency neuronal synchronization. Their activity supports critical developmental trajectories, sensory and cognitive processing, and social behavior. Despite heterogeneity in the etiology across schizophrenia and autism spectrum disorder, PVI circuits are altered in these psychiatric disorders. Identifying mechanism(s) underlying PVI deficits is essential to establish treatments targeting in particular cognition. On the basis of published and new data, we propose oxidative stress as a common pathological mechanism leading to PVI impairment in schizophrenia and some forms of autism. A series of animal models carrying genetic and/or environmental risks relevant …
Trash Removal Methods For Improved Mechanical Emptying Of Pit Latrines Using A Screw Auger.,
2017
NC State University
Trash Removal Methods For Improved Mechanical Emptying Of Pit Latrines Using A Screw Auger., Tracey Sisco, Tate Rogers, Walt Beckwith, Willy Chipeta, Rochelle Holm, Christopher A. Buckley, Francis L. De Los Reyes
Faculty and Staff Scholarship
Trash in pit latrines is one of the largest challenges facing pit emptying technologies, including the powered auger (the Excrevator), developed for improved emptying in lower- and lower-middle income countries. This study focused on two trash removal methods in conjunction with pit emptying by the Excrevator: (1) simultaneous removal of trash with sludge and (2) manual trash removal prior to sludge removal. Simultaneous removal was tested by adding to the inlet of the Excrevator system two cutting heads designed to reduce the size of trash particles before entering the pipe and auger. Laboratory testing indicated that the auger will not …
An Open-Sourced Statistical Application For Identifying Complex Toxicological Interactions Of Environmental Pollutants,
2017
University of Kentucky
An Open-Sourced Statistical Application For Identifying Complex Toxicological Interactions Of Environmental Pollutants, Jordan T. Perkins, Michael C. Petriello, Li Xu, Arnold J. Stromberg, Bernhard Hennig
Superfund Research Center Faculty Publications
The rising number of chemicals that humans are exposed to on a daily basis, as well as advances in biomonitoring and detection technologies have highlighted the diversity of individual exposure profiles (complex body burdens). To address this, the toxicological sciences have begun to shift away from examining toxic agents or stressors individually to focusing on more complex models with multiple agents or stressors present. Literature on interactions between chemicals is fairly limited in comparison with dose-response studies on individual toxicants, which is largely due to experimental and statistical challenges. Experimental designs capable of identifying these complex interactions are often avoided …
Mechanisms Of Thymic Toxicity Induced By Environmentally Relevant Concentrations Of Arsenic,
2017
University of New Mexico
Mechanisms Of Thymic Toxicity Induced By Environmentally Relevant Concentrations Of Arsenic, Huan Xu
Biomedical Sciences ETDs
Arsenic, a ubiquitous environmental contaminant, is known to cause immunotoxicity. However, the mechanisms of arsenic induced immunotoxicity are still not clear. Arsenite (As+3), the trivalent inorganic form of arsenic, was found to increase DNA damage and inhibit PARP activity in thymus cells at 50 nM in vitro. Oxidative stress and double strand breaks (DSBs) formation occurred in thymus cells exposed to As+3 at 500 nM. The genotoxicity was found to be related to As+3 exporter expressions and reversed by zinc supplement. IL-7 signaling, the critical cytokine signal for the early DN thymic T cell proliferation, …
Epigenomic Reprogramming In Inorganic Arsenic-Mediated Gene Expression Patterns During Carcinogenesis,
2017
University of Kentucky
Epigenomic Reprogramming In Inorganic Arsenic-Mediated Gene Expression Patterns During Carcinogenesis, Meredith Eckstein, Rebekah Eleazer, Matthew Rea, Yvonne N. Fondufe-Mittendorf
Molecular and Cellular Biochemistry Faculty Publications
Arsenic is a ubiquitous metalloid that is not mutagenic but is carcinogenic. The mechanism(s) by which arsenic causes cancer remain unknown. To date, several mechanisms have been proposed, including the arsenic-induced generation of reactive oxygen species (ROS). However, it is also becoming evident that inorganic arsenic (iAs) may exert its carcinogenic effects by changing the epigenome, and thereby modifying chromatin structure and dynamics. These epigenetic changes alter the accessibility of gene regulatory factors to DNA, resulting in specific changes in gene expression both at the levels of transcription initiation and gene splicing. In this review, we discuss recent literature reports …
Effect Of Cigarette Smoke Exposure And Mutant Kras Overexpression On Pancreatic Cell Proliferation,
2017
University of Kentucky
Effect Of Cigarette Smoke Exposure And Mutant Kras Overexpression On Pancreatic Cell Proliferation, Howard P. Glauert, R. Scott Elliott, Sung Gu Han, Mark Athey, Eun Young Lee, C. Gary Gairola
Pharmacology and Nutritional Sciences Faculty Publications
Pancreatic cancer is the fourth leading cause of cancer‑associated mortality. The major risk factor for pancreatic cancer is cigarette smoking. Kras mutations are commonly observed in human pancreatic cancers. The present study examined the hypothesis that exposure to cigarette smoke and overexpression of a mutant Kras gene in the pancreas affects pancreatic cell proliferation in mice. Mice overexpressing the mutant Kras gene (KRasG12D) in the pancreas as well as wild‑type mice were exposed to environmental tobacco smoke for 2 weeks. Overexpression of mutant Kras increased cell proliferation in pancreatic ductal, acinar and islet cells. Notably, cigarette smoke exposure …
