Digital Commons Network^™

Epigenetics Of Lipid Phenotypes, Sergi Sayols-Baixeras, Marguerite R. Irvin, Donna K. Arnett, Roberto Elosua, Stella W. Aslibekyan

Epidemiology and Environmental Health Faculty Publications

Dyslipidemia is a well-established risk factor for cardiovascular disease, the main cause of death worldwide. Blood lipid profiles are patterned by both genetic and environmental factors. In recent years, epigenetics has emerged as a paradigm that unifies these influences. In this review, we have summarized the latest evidence implicating epigenetic mechanisms—DNA methylation, histone modification, and regulation by RNAs—in lipid homeostasis. Key findings have emerged in a number of novel epigenetic loci located in biologically plausible genes (eg, CPT1A, ABCG1, SREBF1, and others), as well as microRNA-33a/b. Evidence from animal and cell culture models suggests a complex interplay …

Inhibition Of Human Metapneumovirus Binding To Heparan Sulfate Blocks Infection In Human Lung Cells And Airway Tissues, Edita M. Klimyte, Stacy E. Smith, Pasqua Oreste, David Lembo, Rebecca Ellis Dutch

Molecular and Cellular Biochemistry Faculty Publications

Human metapneumovirus (HMPV), a recently discovered paramyxovirus, infects nearly 100% of the world population and causes severe respiratory disease in infants, the elderly, and immunocompromised patients. We previously showed that HMPV binds heparan sulfate proteoglycans (HSPGs) and that HMPV binding requires only the viral fusion (F) protein. To characterize the features of this interaction critical for HMPV binding and the role of this interaction in infection in relevant models, we utilized sulfated polysaccharides, heparan sulfate mimetics, and occluding compounds. Iota-carrageenan demonstrated potent anti-HMPV activity by inhibiting binding to lung cells mediated by the F protein. Furthermore, analysis of a minilibrary …

Applying Community-Based Participatory Research Partnership Principles To Public Health Practice-Based Research Networks, Nancy L. Winterbauer, Betty Bekemeier, Lisa Vanraemdonck, Anna Goodman Hoover

Preventive Medicine and Environmental Health Faculty Publications

With real-world relevance and translatability as important goals, applied methodological approaches have arisen along the participatory continuum that value context and empower stakeholders to partner actively with academics throughout the research process. Community-based participatory research (CBPR) provides the gold standard for equitable, partnered research in traditional communities. Practice-based research networks (PBRNs) also have developed, coalescing communities of practice and of academics to identify, study, and answer practice-relevant questions. To optimize PBRN potential for expanding scientific knowledge, while bridging divides across knowledge production, dissemination, and implementation, we elucidate how PBRN partnerships can be strengthened by applying CBPR principles to build and …

An Arginine Finger Regulates The Sequential Action Of Asymmetrical Hexameric Atpase In The Double-Stranded Dna Translocation Motor, Zhengyi Zhao, Gian Marco De-Donatis, Chad T. Schwartz, Huaming Fang, Jingyuan Li, Peixuan Guo

Pharmaceutical Sciences Faculty Publications

Biological motors are ubiquitous in living systems. Currently, how the motor components coordinate the unidirectional motion is elusive in most cases. Here, we report that the sequential action of the ATPase ring in the DNA packaging motor of bacteriophage ϕ29 is regulated by an arginine finger that extends from one ATPase subunit to the adjacent unit to promote noncovalent dimer formation. Mutation of the arginine finger resulted in the interruption of ATPase oligomerization, ATP binding/hydrolysis, and DNA translocation. Dimer formation reappeared when arginine mutants were mixed with other ATPase subunits that can offer the arginine to promote their interaction. Ultracentrifugation …

Improving A Dental School's Clinic Operations Using Lean Process Improvement, Fonda G. Robinson, Larry L. Cunningham, Sharon P. Turner, John E. Lindroth, Deborah Ray, Talib Khan, Audrey Yates

Oral Health Practice Faculty Publications

The term "lean production," also known as "Lean," describes a process of operations management pioneered at the Toyota Motor Company that contributed significantly to the success of the company. Although developed by Toyota, the Lean process has been implemented at many other organizations, including those in health care, and should be considered by dental schools in evaluating their clinical operations. Lean combines engineering principles with operations management and improvement tools to optimize business and operating processes. One of the core concepts is relentless elimination of waste (non-value-added components of a process). Another key concept is utilization of individuals closest to …

Using Low-Dose Radiation To Potentiate The Effect Of Induction Chemotherapy In Head And Neck Cancer: Results Of A Prospective Phase 2 Trial, Susanne M. Arnold, Mahesh Kudrimoti, Emily V. Dressler, John F. Gleason, Natalie L. Silver, William F. Regine, Joseph Valentino

Internal Medicine Faculty Publications

Purpose: Low-dose fractionated radiation therapy (LDFRT) induces effective cell killing through hyperradiation sensitivity and potentiates effects of chemotherapy. We report our second investigation of LDFRT as a potentiator of the chemotherapeutic effect of induction carboplatin and paclitaxel in locally advanced squamous cell cancer of the head and neck (SCCHN).

Experimental Design: Two cycles of induction therapy were given every 21 days: paclitaxel (75 mg/m²) on days 1, 8, and 15; carboplatin (area under the curve 6) day 1; and LDFRT 50 cGy fractions (2 each on days 1, 2, 8, and 15). Objectives included primary site complete response …

Pharmacology Of Cannabis, Mandakini Sadhir

Pediatrics Faculty Publications

Cannabis has been used for recreational purposes around the world. It is derived from the plant cannabis sativa which has various other compounds known as cannabinoids. Most common form of cannabis used for recreational purpose is marijuana, which is prepared from dried flowering tops and leaves. The primary psychoactive component is delta 9-tetrahydrocannabinol (δ-9THC), which exerts its physiological and psychological effects through its interaction with CB1 and CB2 receptors. Smoking is the most commonly used method with onset of effects within minutes after inhalation. Oral ingestion of cannabis has varied absorption with delayed onset but longer duration of action. Urine …

Neuromuscular Alterations After Ankle Sprains: An Animal Model To Establish Causal Links After Injury, Lindsey K. Lepley, Patrick O. Mckeon, Shane G. Fitzpatrick, Catherine L. Beckemeyer, Timothy L. Uhl, Timothy A. Butterfield

Physical Therapy Faculty Publications

Context: The mechanisms that contribute to the development of chronic ankle instability are not understood. Investigators have developed a hypothetical model in which neuromuscular alterations that stem from damaged ankle ligaments are thought to affect periarticular and proximal muscle activity. However, the retrospective nature of these studies does not allow a causal link to be established.

Objective: To assess temporal alterations in the activity of 2 periarticular muscles of the rat ankle and 2 proximal muscles of the rat hind limb after an ankle sprain.

Design: Controlled laboratory study.

Setting: Laboratory.

Patients or Other Participants: …

Talin2-Mediated Traction Force Drives Matrix Degradation And Cell Invasion, Lei Qi, Naser Jafari, Xiang Li, Zaozao Chen, Liqing Li, Vesa P. Hytönen, Benjamin T. Goult, Chang-Guo Zhan, Cai Huang

Markey Cancer Center Faculty Publications

Talin binds to β-integrin tails to activate integrins, regulating cell migration, invasion and metastasis. There are two talin genes, TLN1 and TLN2, encoding talin1 and talin2, respectively. Talin1 regulates focal adhesion dynamics, cell migration and invasion, whereas the biological function of talin2 is not clear and, indeed, talin2 has been presumed to function redundantly with talin1. Here, we show that talin2 has a much stronger binding to β-integrin tails than talin1. Replacement of talin2 Ser339 with Cys significantly decreased its binding to β1-integrin tails to a level comparable to that of talin1. Talin2 localizes at invadopodia and is indispensable …

Weighted-Samgsr: Combining Significance Analysis Of Microarray-Gene Set Reduction Algorithm With Pathway Topology-Based Weights To Select Relevant Genes, Suyan Tian, Howard H. Chang, Chi Wang

Biostatistics Faculty Publications

Background: It has been demonstrated that a pathway-based feature selection method that incorporates biological information within pathways during the process of feature selection usually outperforms a gene-based feature selection algorithm in terms of predictive accuracy and stability. Significance analysis of microarray-gene set reduction algorithm (SAMGSR), an extension to a gene set analysis method with further reduction of the selected pathways to their respective core subsets, can be regarded as a pathway-based feature selection method.

Methods: In SAMGSR, whether a gene is selected is mainly determined by its expression difference between the phenotypes, and partially by the number of pathways to …

Human Metapneumovirus Induces Reorganization Of The Actin Cytoskeleton For Direct Cell-To-Cell Spread, Farah El Najjar, Nicolás Cifuentes-Muñoz, Jing Chen, Haining Zhu, Ursula J. Buchholz, Carole L. Moncman, Rebecca Ellis Dutch

Molecular and Cellular Biochemistry Faculty Publications

Paramyxovirus spread generally involves assembly of individual viral particles which then infect target cells. We show that infection of human bronchial airway cells with human metapneumovirus (HMPV), a recently identified paramyxovirus which causes significant respiratory disease, results in formation of intercellular extensions and extensive networks of branched cell-associated filaments. Formation of these structures is dependent on actin, but not microtubule, polymerization. Interestingly, using a co-culture assay we show that conditions which block regular infection by HMPV particles, including addition of neutralizing antibodies or removal of cell surface heparan sulfate, did not prevent viral spread from infected to new target cells. …

Protection Of Cells From Alu-Rna-Induced Degeneration And Inhibitors For Protecting Cells, Jayakrishna Ambati, Valeria Tarallo

Ophthalmology and Visual Science Faculty Patents

A method of protecting a cell includes inhibiting an inflammasome, MyD88, IL-18, VDAC1, VDAC2, caspase-8, and/or NFκB of the cell. Administering an inhibitor of MyD88, IL-18, VDAC1, VDAC2, caspase-8, and/or NFκB can protect the cell from Alu-RNA-induced degeneration. Protecting a cell, such as an retinal pigment epithelium (RPE), can be therapeutically useful in the context of age-related macular degeneration and geographic atrophy.

Identification Of Control Targets In Boolean Molecular Network Models Via Computational Algebra, David Murrugarra, Alan Veliz-Cuba, Boris Aguilar, Reinhard Laubenbacher

Mathematics Faculty Publications

Background: Many problems in biomedicine and other areas of the life sciences can be characterized as control problems, with the goal of finding strategies to change a disease or otherwise undesirable state of a biological system into another, more desirable, state through an intervention, such as a drug or other therapeutic treatment. The identification of such strategies is typically based on a mathematical model of the process to be altered through targeted control inputs. This paper focuses on processes at the molecular level that determine the state of an individual cell, involving signaling or gene regulation. The mathematical model type …

Immunomodulators As Therapeutic Agents In Mitigating The Progression Of Parkinson's Disease, Bethany Grimmig, Josh Morganti, Kevin Nash, Paula C. Bickford

Sanders-Brown Center on Aging Faculty Publications

Parkinson’s disease (PD) is a common neurodegenerative disorder that primarily afflicts the elderly. It is characterized by motor dysfunction due to extensive neuron loss in the substantia nigra pars compacta. There are multiple biological processes that are negatively impacted during the pathogenesis of PD, and are implicated in the cell death in this region. Neuroinflammation is evidently involved in PD pathology and mitigating the inflammatory cascade has been a therapeutic strategy. Age is the number one risk factor for PD and thus needs to be considered in the context of disease pathology. Here, we discuss the role of neuroinflammation within …

Female Adult Aedes Albopictus Suppression By Wolbachia-Infected Male Mosquitoes, James W. Mains, Corey L. Brelsfoard, Robert I. Rose, Stephen L. Dobson

Entomology Faculty Publications

Dengue, chikungunya and zika viruses are pathogens with an increasing global impact. In the absence of an approved vaccine or therapy, their management relies on controlling the mosquito vectors. But traditional controls are inadequate, and the range of invasive species such as Aedes albopictus (Asian Tiger Mosquito) is expanding. Genetically modified mosquitoes are being tested, but their use has encountered regulatory barriers and public opposition in some countries. Wolbachia bacteria can cause a form of conditional sterility, which can provide an alternative to genetic modification or irradiation. It is unknown however, whether openly released, artificially infected male Ae. albopictus can …

Extracellular Vesicle-Associated Aβ Mediates Trans-Neuronal Bioenergetic And Ca2+-Handling Deficits In Alzheimer's Disease Models, Erez Eitan, Emmette R. Hutchison, Krisztina Marosi, James Comotto, Maja Mustapic, Saket M. Nigam, Caitlin Suire, Chinmoyee Maharana, Gregory A. Jicha, Dong Liu, Vasiliki Machairaki, Kenneth W. Witwer, Dimitrios Kapogiannis, Mark P. Mattson

Sanders-Brown Center on Aging Faculty Publications

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder in which aggregation-prone neurotoxic amyloid β-peptide (Aβ) accumulates in the brain. Extracellular vesicles (EVs), including exosomes, are small 50–150 nm membrane vesicles that have recently been implicated in the prion-like spread of self-aggregating proteins. Here we report that EVs isolated from AD patient cerebrospinal fluid and plasma, from the plasma of two AD mouse models, and from the medium of neural cells expressing familial AD presenilin 1 mutations, destabilize neuronal Ca²⁺ homeostasis, impair mitochondrial function, and sensitize neurons to excitotoxicity. EVs contain a relatively low amount of Aβ but have an …

Cycle Training Modulates Satellite Cell And Transcriptional Responses To A Bout Of Resistance Exercise, Kevin A. Murach, R. Grace Walton, Christopher S. Fry, Sami L. Michaelis, Jason S. Groshong, Brian S. Finlin, Philip A. Kern, Charlotte A. Peterson

Clinical and Translational Science Faculty Publications

This investigation evaluated whether moderate-intensity cycle ergometer training affects satellite cell and molecular responses to acute maximal concentric/eccentric resistance exercise in middle-aged women. Baseline and 72 h postresistance exercise vastus lateralis biopsies were obtained from seven healthy middle-aged women (56 ± 5 years, BMI 26 ± 1, VO_2max 27 ± 4) before and after 12 weeks of cycle training. Myosin heavy chain (MyHC) I- and II-associated satellite cell density and cross-sectional area was determined via immunohistochemistry. Expression of 93 genes representative of the muscle-remodeling environment was also measured via NanoString. Overall fiber size increased ~20% with cycle training ( …

Use Of Parthenolide Derivatives As Antileukemic And Cytotoxic Agents, Peter A. Crooks, Craig T. Jordan, Xiaochen Wei

Pharmaceutical Sciences Faculty Patents

To read this abstract, please download this patent.

Semi-Synthetic Mithramycin Derivatives With Anti-Cancer Activity, Jürgen Rohr, Daniel Scott, Markos Leggas, Jhong-Min Chen, Oleg V. Tsodikov

Pharmaceutical Sciences Faculty Patents

Mithramycin derivatives and their pharmaceutically acceptable salts are disclosed. The mithramycin derivatives can be used in the treatment of Ewing sarcoma or other cancer or neuro-disease associated with an aberrant erythroblast transformation- specific transcription factor.

Airway Secretory Micrornaome Changes During Rhinovirus Infection In Early Childhood, Maria J. Gutierrez, Jose L. Gomez, Geovanny F. Perez, Krishna Pancham, Stephanie Val, Dinesh K. Pillai, Mamta Giri, Sarah Ferrante, Robert Freishtat, Mary C. Rose, Diego Preciado, Gustavo Nino

Pediatrics Faculty Publications

Background Innate immune responses are fine-tuned by small noncoding RNA molecules termed microRNAs (miRs) that modify gene expression in response to the environment. During acute infections, miRs can be secreted in extracellular vesicles (EV) to facilitate cell-to-cell genetic communication. The purpose of this study was to characterize the baseline population of miRs secreted in EVs in the airways of young children (airway secretory microRNAome) and examine the changes during rhinovirus (RV) infection, the most common cause of asthma exacerbations and the most important early risk factor for the development of asthma beyond childhood.

Methods Nasal airway secretions were obtained from …

Cycle Training Modulates Satellite Cell And Transcriptional Responses To A Bout Of Resistance Exercise, Kevin A. Murach, R. Grace Walton, Christopher S. Fry, Sami L. Michaelis, Jason S. Groshong, Brian S. Finlin, Philip A. Kern, Charlotte A. Peterson

Physical Therapy Faculty Publications

This investigation evaluated whether moderate‐intensity cycle ergometer training affects satellite cell and molecular responses to acute maximal concentric/eccentric resistance exercise in middle‐aged women. Baseline and 72 h postresistance exercise vastus lateralis biopsies were obtained from seven healthy middle‐aged women (56 ± 5 years, BMI 26 ± 1, VO_2max 27 ± 4) before and after 12 weeks of cycle training. Myosin heavy chain (MyHC) I‐ and II‐associated satellite cell density and cross‐sectional area was determined via immunohistochemistry. Expression of 93 genes representative of the muscle‐remodeling environment was also measured via NanoString. Overall fiber size increased ~20% with cycle training ( …

Comparative Analysis Of Linker Histone H1, Mecp2, And Hmgd1 On Nucleosome Stability And Target Site Accessibility, Caitlyn Riedmann, Yvonne N. Fondufe-Mittendorf

Molecular and Cellular Biochemistry Faculty Publications

Chromatin architectural proteins (CAPs) bind the entry/exit DNA of nucleosomes and linker DNA to form higher order chromatin structures with distinct transcriptional outcomes. How CAPs mediate nucleosome dynamics is not well understood. We hypothesize that CAPs regulate DNA target site accessibility through alteration of the rate of spontaneous dissociation of DNA from nucleosomes. We investigated the effects of histone H1, high mobility group D1 (HMGD1), and methyl CpG binding protein 2 (MeCP2), on the biophysical properties of nucleosomes and chromatin. We show that MeCP2, like the repressive histone H1, traps the nucleosome in a more compact mononucleosome structure. Furthermore, histone …

Methamphetamine: A Substance Of Emerging Environmental Concern For Horse Racing, Clara Fenger, Tanya Boulmetis, Kim Brewer, Kent Stirling, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

No abstract provided.

Grain Boundary Induced Bias Instability In Soluble Acene-Based Thin-Film Transistors, Ky V. Nguyen, Marcia M. Payne, John E. Anthony, Jung Hun Lee, Eunjoo Song, Boseok Kang, Kilwon Cho, Wi Hyoung Lee

Chemistry Faculty Publications

Since the grain boundaries (GBs) within the semiconductor layer of organic field-effect transistors (OFETs) have a strong influence on device performance, a substantial number of studies have been devoted to controlling the crystallization characteristics of organic semiconductors. We studied the intrinsic effects of GBs within 5,11-bis(triethylsilylethynyl) anthradithiophene (TES-ADT) thin films on the electrical properties of OFETs. The GB density was easily changed by controlling nulceation event in TES-ADT thin films. When the mixing time was increased, the number of aggregates in as-spun TES-ADT thin films were increased and subsequent exposure of the films to 1,2-dichloroethane vapor led to a significant …

Use Of Several Natural Products From Selected Nicotiana Species To Prevent Black Shank Disease In Tobacco, Antoaneta B. Kroumova, Ivan Artiouchine, George J. Wagner

Kentucky Tobacco Research and Development Center Faculty Publications

Black shank is a major annual disease threat to all types of tobacco worldwide. It is caused by the fungus Phytophthora parasitica var. nicotianae (PPN). The major tobacco growing areas in US - Kentucky, Tennessee and North Carolina can experience devastating losses, reaching in some fields up to 100%. Thus far, the main approaches to control this disease have been creation of resistant varieties, fungicide treatments, and crop rotation. Some fungicides are reported to have negative effects on the environment. The goal of this work was to test the antifungal activity of several natural products that are synthesized by certain …

Polymeric Prodrug, David A. Puleo, Thomas D. Dziubla, Theodora Asafo-Adjei

Biomedical Engineering Faculty Patents

The presently-disclosed subject matter includes compounds that comprise an initiator and an active agent that is covalently bonded to the initiator through a ring-opening polymerization process, an atom-transfer radical polymerization process, a Michael addition reaction, or a ring-opening metathesis polymerization process. In some embodiments the active agent includes simvastatin. The presently-disclosed subject matter also includes methods for making the compositions and methods for using the compositions to treat tissue wounds.

Century-Long Increasing Trend And Variability Of Dissolved Organic Carbon Export From The Mississippi River Basin Driven By Natural And Anthropogenic Forcing, Wei Ren, Hanqin Tian, Wei-Jun Cai, Steven E. Lohrenz, Charles S. Hopkinson, Wei-Jen Huang, Jia Yang, Bo Tao, Shufen Pan, Ruoying He

Plant and Soil Sciences Faculty Publications

There has been considerable debate as to how natural forcing and anthropogenic activities alter the timing and magnitude of the delivery of dissolved organic carbon (DOC) to the coastal ocean, which has ramifications for the ocean carbon budget, land-ocean interactions, and coastal life. Here we present an analysis of DOC export from the Mississippi River to the Gulf of Mexico during 1901–2010 as influenced by changes in climate, land use and management practices, atmospheric CO₂, and nitrogen deposition, through the integration of observational data with a coupled hydrologic/biogeochemical land model. Model simulations show that DOC export in the …

Methane Emissions From Global Rice Fields: Magnitude, Spatiotemporal Patterns, And Environmental Controls, Bowen Zhang, Hanqin Tian, Wei Ren, Bo Tao, Chaoqun Lu, Jia Yang, Kamaljit Banger, Shufen Pan

Plant and Soil Sciences Faculty Publications

Given the importance of the potential positive feedback between methane (CH₄) emissions and climate change, it is critical to accurately estimate the magnitude and spatiotemporal patterns of CH₄ emissions from global rice fields and better understand the underlying determinants governing the emissions. Here we used a coupled biogeochemical model in combination with satellite-derived contemporary inundation area to quantify the magnitude and spatiotemporal variation of CH₄ emissions from global rice fields and attribute the environmental controls of CH₄ emissions during 1901–2010. Our study estimated that CH₄ emissions from global rice fields varied from 18.3 ± …

How Did The Aca Affect Health Insurance Coverage In Kentucky?, Aaron Yelowitz

Institute for the Study of Free Enterprise Working Papers

The major components of the Affordable Care Act (ACA) were implemented in 2014, including the rollout of the Health Insurance Marketplace, Medicaid expansions, and the individual mandate. Kentucky stands out as one of the few southern states to expand Medicaid, and earlier work has demonstrated that Kentucky experienced some of the largest gains in health insurance coverage. The goal of the current study is to further explore the sources that individuals used to gain coverage in Kentucky using a large, publicly available dataset, the American Community Survey (ACS). Several findings emerge. First, overall health insurance coverage increased by 5.7 percentage …

Improving Human Papillomavirus Immunization Rates In Kentucky, Nneka S. Udechukwu, Paul Duffin, Alissa Briggs, Hatim A. Omar

Pediatrics Faculty Publications

No abstract provided.