Digital Commons Network^™

Apolipoprotein E4 Alters Astrocyte Fatty Acid Metabolism And Lipid Droplet Formation, Brandon C. Farmer, Jude Kluemper, Lance A. Johnson

Physiology Faculty Publications

Lipid droplets (LDs) serve as energy rich reservoirs and have been associated with apolipoprotein E (APOE) and neurodegeneration. The E4 allele of APOE (E4) is the strongest genetic risk factor for the development of late onset Alzheimer’s disease (AD). Since both E4 carriers and individuals with AD exhibit a state of cerebral lipid dyshomeostasis, we hypothesized that APOE may play a role in regulating LD metabolism. We found that astrocytes expressing E4 accumulate significantly more and smaller LDs compared to E3 astrocytes. Accordingly, expression of perilipin-2, an essential LD protein component, was higher in E4 astrocytes. We then …

Eis Inhibitors, Sylvie Garneau-Tsodikova, Oleg V. Tsodikov, James E. Posey

Pharmaceutical Sciences Faculty Patents

Provided herein are novel small-molecules that have use in the inhibition of Eis, which mediates kanamycin resistance in Mycobacterium tuberculosis. The presently-disclosed subject matter further includes a pharmaceutical composition including a small molecule inhibitor, as described herein, and a suitable pharmaceutical carrier. Methods of treating tuberculosis comprising administering to an individual an effective amount of the disclosed small molecule inhibitors to mediate kanamycin A resistance and treat tuberculosis are also provided.

Why Ask Why?, Beth Kraemer, Beth Fuchs, Jennifer Hootman, Debbie Sharp

Greater Faculties: A Review of Teaching and Learning

No abstract provided.

The Future Of The History Of Design, Patrick Lucas, Helen Turner, Trey Conatser

Greater Faculties: A Review of Teaching and Learning

No abstract provided.

Teaching Stem For The Public Good, Rita Basuray

Greater Faculties: A Review of Teaching and Learning

No abstract provided.

The Limits Of Pedagogy, Kelsey Moore

Greater Faculties: A Review of Teaching and Learning

No abstract provided.

On Rapport: Connecting With Students, Brandi Frisby

Greater Faculties: A Review of Teaching and Learning

No abstract provided.

Ten First Years, Jennifer Osterhage

Greater Faculties: A Review of Teaching and Learning

No abstract provided.

Diagnostic Dilemma Of Disseminated Histoplasmosis Mimicking Hemophagocytosis Lymphohistiocytosis In Patient With Rheumatoid Arthritis On Anti-Tnf Therapy: Case Report And Review Of The Literature, Saurav Suman, Aleksander Lenert

Internal Medicine Faculty Publications

Tumor necrosis factor inhibitors (TNFi) have become the cornerstone for the treatment of rheumatoid arthritis and other systemic autoimmune conditions. However, these biologic DMARDs can lead to various opportunistic infections such as viral infection, tuberculosis, and histoplasmosis. Furthermore, these biologics can also cause severe systemic inflammatory reactions known as hemophagocytosis lymphohistiocytosis (HLH) that can lead to multiorgan failure and high mortality. Due to overlapping clinical features and time-intensive microbiological culture methods, distinguishing between HLH and opportunistic infections can be challenging early in the disease course. We present a similar situation with our patient where the patient met the diagnostic criteria …

Carboxylic Acids Accelerate Acidic Environment-Mediated Nanoceria Dissolution, Robert A. Yokel, Matthew L. Hancock, Eric A. Grulke, Jason M. Unrine, Alan K. Dozier, Uschi M. Graham

Pharmaceutical Sciences Faculty Publications

Ligands that accelerate nanoceria dissolution may greatly affect its fate and effects. This project assessed the carboxylic acid contribution to nanoceria dissolution in aqueous, acidic environments. Nanoceria has commercial and potential therapeutic and energy storage applications. It biotransforms in vivo. Citric acid stabilizes nanoceria during synthesis and in aqueous dispersions. In this study, citrate-stabilized nanoceria dispersions (∼4 nm average primary particle size) were loaded into dialysis cassettes whose membranes passed cerium salts but not nanoceria particles. The cassettes were immersed in iso-osmotic baths containing carboxylic acids at pH 4.5 and 37 °C, or other select agents. Cerium atom material …

Teach Students, Empower Patients, Act Collaboratively And Meet Health Goals: An Early Interprofessional Clinical Experience In Transformed Care, Maria Gabriela Castro, Melanie Dicks, Keisa Bennett, Carol Hustedde, David Sacks, Lynn Joyce Hunter, William Elder

Family and Community Medicine Faculty Publications

Purpose: Transformation of care teaching is often didactic and conceptual instead of practical and operational. Clinical environments, slow to transform, limit student exposure to key experiences that characterize transformed care. We describe the design and implementation of TEAM Clinic (Teach students, Empower patients, Act collaboratively, Meet health goals) – an early clinical learning experience to address this gap.

Methods: The TEAM Clinic curriculum was based on a review of existing curricula and best practice recommendations for the transformation of care. Three key elements were selected as the focus for a low-volume, high-service clinic: patient centeredness, interprofessional collaboration and team-based care. …

Increasing Salt Rejection Of Polybenzimidazole Nanofiltration Membranes Via The Addition Of Immobilized And Aligned Aquaporins, Priyesh Ashokrao Wagh, Xinyi Zhang, Ryan Blood, Peter M. Kekenes-Huskey, Prasangi Rajapaksha, Yinan Wei, Isabel C. Escobar

Chemical and Materials Engineering Faculty Publications

Aquaporins are water channel proteins in cell membrane, highly specific for water molecules while restricting the passage of contaminants and small molecules, such as urea and boric acid. Cysteine functional groups were installed on aquaporin Z for covalent attachment to the polymer membrane matrix so that the proteins could be immobilized to the membranes and aligned in the direction of the flow. Depth profiling using x-ray photoelectron spectrometer (XPS) analysis showed the presence of functional groups corresponding to aquaporin Z modified with cysteine (Aqp-SH). Aqp-SH modified membranes showed a higher salt rejection as compared to unmodified membranes. For 2 M …

An Economic Feasibility Assessment Of Autonomous Field Machinery In Grain Crop Production, Jordan Murphy Shockley, Carl R. Dillon, Scott A. Shearer

Agricultural Economics Faculty Publications

A multi-faceted whole farm planning model is developed to compare conventional and autonomous machinery for grain crop production under various benefit, farm size, suitable field day risk aversion, and grain price scenarios. Results suggest that autonomous machinery can be an economically viable alternative to conventional manned machinery if the establishment of intelligent controls is cost effective. An increase in net returns of 24% over operating with conventional machinery is found when including both input savings and a yield increase due to reduced compaction. This study also identifies the break-even investment price for intelligent controls for the safe and reliable commercialization …

The Three-Year Impact Of The Affordable Care Act On Disparities In Insurance Coverage, Charles J. Courtemanche, James Marton, Benjamin Ukert, Aaron Yelowitz, Daniela Zapata, Ishtiaque Fazlul

Economics Faculty Publications

Objective
To estimate the impact of the major components of the ACA (Medicaid expansion, subsidized Marketplace plans, and insurance market reforms) on disparities in insurance coverage after three years.

Data Source
The 2011-2016 waves of the American Community Survey (ACS), with the sample restricted to nonelderly adults.

Design
We estimate a difference-in-difference-in-differences model to separately identify the effects of the nationwide and Medicaid expansion portions of the ACA using the methodology developed in the recent ACA literature. The differences come from time, state Medicaid expansion status, and local area pre-ACA uninsured rates. In order to focus on access disparities, we …

The Digital Knowledge Economy Index: Mapping Content Production, Sanna Ojanperä, Mark Graham, Matthew Zook

Geography Faculty Publications

We propose the construction of a Digital Knowledge Economy Index, quantified by way of measuring content creation and participation through digital platforms, namely the code sharing platform GitHub, the crowdsourced encyclopaedia Wikipedia, and Internet domain registrations and estimating a fifth sub-index for the World Bank Knowledge Economy Index for year 2012. This approach complements conventional data sources such as national statistics and expert surveys and helps reflect the underlying digital content creation, capacities, and skills of the population. An index that combines traditional and novel data sources can provide a more revealing view of the status of the world’s digital …

Immunization Of Alpacas (Lama Pacos) With Protein Antigens And Production Of Antigen-Specific Single Domain Antibodies, K. Martin Chow, Sidney W. Whiteheart, Jeffrey R. Smiley, Savita Sharma, Kathy Boaz, Meggie J. Coleman, Alvina Maynard, Louis B. Hersh, Craig W. Vander Kooi

Molecular and Cellular Biochemistry Faculty Publications

In this manuscript, a method for the immunization of alpaca and the use of molecular biology methods to produce antigen-specific single domain antibodies is described and demonstrated. Camelids, such as alpacas and llamas, have become a valuable resource for biomedical research since they produce a novel type of heavy chain-only antibody which can be used to produce single domain antibodies. Because the immune system is highly flexible, single domain antibodies can be made to many different protein antigens, and even different conformations of the antigen, with a very high degree of specificity. These features, among others, make single domain antibodies …

Itch Nuclear Translocation And H1.2 Polyubiquitination Negatively Regulate The Dna Damage Response, Lufen Chang, Lei Shen, Hu Zhou, Jing Gao, Hangyi Pan, Li Zheng, Brian Armstrong, Yang Peng, Guang Peng, Binhua P. Zhou, Steven T. Rosen, Binghui Shen

Molecular and Cellular Biochemistry Faculty Publications

The downregulation of the DNA damage response (DDR) enables aggressive tumors to achieve uncontrolled proliferation against replication stress, but the mechanisms underlying this process in tumors are relatively complex. Here, we demonstrate a mechanism through which a distinct E3 ubiquitin ligase, ITCH, modulates DDR machinery in triple-negative breast cancer (TNBC). We found that expression of a nuclear form of ITCH was significantly increased in human TNBC cell lines and tumor specimens. Phosphorylation of ITCH at Ser257 by AKT led to the nuclear localization of ITCH and ubiquitination of H1.2. The ITCH-mediated polyubiquitination of H1.2 suppressed RNF8/RNF168-dependent formation of 53BP1 foci, …

Absence Of Endothelial Α5Β1 Integrin Triggers Early Onset Of Experimental Autoimmune Encephalomyelitis Due To Reduced Vascular Remodeling And Compromised Vascular Integrity, Ravi Kant, Sebok K. Halder, Gregory J. Bix, Richard Milner

Sanders-Brown Center on Aging Faculty Publications

Early in the development of multiple sclerosis (MS) and its mouse model experimental autoimmune encephalomyelitis (EAE), vascular integrity is compromised. This is accompanied by a marked vascular remodeling response, though it is currently unclear whether this is an adaptive vascular repair mechanism or is part of the pathogenic process. In light of the well-described angiogenic role for the α5β1 integrin, the goal of this study was to evaluate how genetic deletion of endothelial α5 integrin (α5-EC-KO mice) impacts vascular remodeling and repair following vascular disruption during EAE pathogenesis, and how this subsequently influences clinical progression and inflammatory demyelination. Immunofluorescence staining …

Cerebrovascular Smooth Muscle Cells As The Drivers Of Intramural Periarterial Drainage Of The Brain, Roxana Aldea, Roy O. Weller, Donna M. Wilcock, Roxana O Carare, Giles Richardson

Physiology Faculty Publications

The human brain is the organ with the highest metabolic activity but it lacks a traditional lymphatic system responsible for clearing waste products. We have demonstrated that the basement membranes of cerebral capillaries and arteries represent the lymphatic pathways of the brain along which intramural periarterial drainage (IPAD) of soluble metabolites occurs. Failure of IPAD could explain the vascular deposition of the amyloid-beta protein as cerebral amyloid angiopathy (CAA), which is a key pathological feature of Alzheimer's disease. The underlying mechanisms of IPAD, including its motive force, have not been clarified, delaying successful therapies for CAA. Although arterial pulsations from …

Multi-Ancestry Study Of Blood Lipid Levels Identifies Four Loci Interacting With Physical Activity, Tuomas O. Kilpeläinen, Amy R. Bentley, Raymond Noordam, Yun Ju Sung, Karen Schwander, Thomas W. Winkler, Hermina Jakupović, Daniel I. Chasman, Alisa Manning, Ioanna Ntalla, Hugues Aschard, Michael R. Brown, Lisa De Las Fuentes, Nora Franceschini, Xiuqing Guo, Dina Vojinovic, Stella Aslibekyan, Mary F. Feitosa, Minjung Kho, Solomon K. Musani, Melissa Richard, Heming Wang, Zhe Wang, Traci M. Bartz, Lawrence F. Bielak, Archie Campbell, Rajkumar Dorajoo, Virginia Fisher, Fernando P. Hartwig, Andrea R. V. R. Horimoto, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL …

Use Of A Cross-Sectional Survey In The Adult Population To Characterize Persons At High-Risk For Chronic Obstructive Pulmonary Disease, Roy A. Pleasants, Khosrow Heidari, Jill Ohar, James F. Donohue, Njira Lugogo, Chelsea L. Richard, Sarojina Kanotra, David M. Mannino, Monica Kraft, Winston Liao, Charlie Strange

Internal Medicine Faculty Publications

Rationale/Objective: The Behavioral Risk Factor Surveillance System (BRFSS) health survey has been used to describe the epidemiology of chronic obstructive pulmonary disease (COPD) in the US. Through addressing respiratory symptoms and tobacco use, it could also be used to characterize COPD risk. Methods: Four US states added questions to the 2015 BRFSS regarding productive cough, shortness of breath, dyspnea on exertion, and tobacco duration. We determined COPD risk categories: provider-diagnosed COPD as self-report, high-risk for COPD as ≥ 10 years tobacco smoking and at least one significant respiratory symptom, and low risk was neither diagnosed COPD nor high risk. Disease …

Coatings On Mammalian Cells: Interfacing Cells With Their Environment, Kara A. Davis, Pei-Jung Wu, Calvin F. Cahall, Cong Li, Anuhya Gottipati, Brad J. Berron

Chemical and Materials Engineering Faculty Publications

The research community is intent on harnessing increasingly complex biological building blocks. At present, cells represent a highly functional component for integration into higher order systems. In this review, we discuss the current application space for cellular coating technologies and emphasize the relationship between the target application and coating design. We also discuss how the cell and the coating interact in common analytical techniques, and where caution must be exercised in the interpretation of results. Finally, we look ahead at emerging application areas that are ideal for innovation in cellular coatings. In all, cellular coatings leverage the machinery unique to …

Generalized Gibbs Ensemble Of 2d Cfts At Large Central Charge In The Thermodynamic Limit, Anatoly Dymarsky, Kirill Pavlenko

Physics and Astronomy Faculty Publications

We discuss partition function of 2d CFTs decorated by higher qKdV charges in the thermodynamic limit when the size of the spatial circle goes to infinity. In this limit the saddle point approximation is exact and at infinite central charge generalized partition function can be calculated explicitly. We show that leading 1/c corrections to free energy can be reformulated as a sum over Young tableaux which we calculate for the first two qKdV charges. Next, we compare generalized ensemble with the “eigenstate ensemble” that consists of a single primary state. At infinite central charge the ensembles match at the …

The Politics Of Richard Wright, Jane Anna Gordon, Cyrus Ernesto Zirakzadeh

Civil Rights

A pillar of African American literature, Richard Wright is one of the most celebrated and controversial authors in American history. His work championed intellectual freedom amid social and political chaos. Despite the popular and critical success of books such as Uncle Tom's Children (1938), Black Boy (1945), and Native Son (1941), Wright faced staunch criticism and even censorship throughout his career for the graphic sexuality, intense violence, and communist themes in his work. Yet, many political theorists have ignored his radical ideas.

In The Politics of Richard Wright, an interdisciplinary group of scholars embraces the controversies surrounding Wright as …

Southern History On Screen, Bryan M. Jack

Civil Rights

Hollywood films have been influential in the portrayal and representation of race relations in the South and how African Americans are cinematically depicted in history, from The Birth of a Nation (1915) and Gone with the Wind (1939) to The Help (2011) and 12 Years a Slave (2013). With an ability to reach mass audiences, films represent the power to influence and shape the public's understanding of our country's past, creating lasting images—both real and imagined—in American culture.

In Southern History on Screen: Race and Rights, 1976–2016, editor Bryan Jack brings together essays from an international roster of scholars …

Star-Related Lipid Transfer Protein 10 (Stard10): A Novel Key Player In Alcohol-Induced Breast Cancer Progression, Andrea Floris, Jia Luo, Jacqueline A. Frank, Jennifer Zhou, Sandro Orrù, Michela Biancolella, Sabina Pucci, Augusto Orlandi, Paolo Campagna, Antonella Balzano, Komal Ramani, Maria Lauda Tomasi

Pharmacology and Nutritional Sciences Faculty Publications

Background: Ethanol abuse promotes breast cancer development, metastasis and recurrence stimulating mammary tumorigenesis by mechanisms that remain unclear. Normally, 35% of breast cancer is Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2)-positive that predisposes to poor prognosis and relapse, while ethanol drinking leads to invasion of their ERBB2 positive cells triggering the phosphorylation status of mitogen-activated protein kinase. StAR-related lipid transfer protein 10 (STARD10) is a lipid transporter of phosphatidylcholine (PC) and phosphatidylethanolamine (PE); changes on membrane composition of PC and PE occur before the morphological tumorigenic events. Interestingly, STARD10 has been described to be highly expressed in 35–40% of ERBB2-positive breast …

Standardizing The Law On Working Animals, Mallie A. Myers

Kentucky Journal of Equine, Agriculture, & Natural Resources Law

No abstract provided.

Tanglewood Trail Walking And Voucher Program, Kelci Marie Mchugh

Theses and Dissertations--Nutrition and Food Systems

Rural Appalachian populations have greater rates of obesity and chronic diseases attributed to lesser consumption of fruits and vegetables (F/V) and physical inactivity. Barriers to F/V consumption and physical activity include poor access and affordability. To help overcome these barriers, a community-initiated walking and farmers market F/V voucher program was implemented.

Participants were encouraged to walk (1.2 miles roundtrip) to the local farmers market to redeem a $10 voucher which could only be spent on F/V. The 16-week program (June – Sept) included 121 participants. Data was analyzed by creating two groups, low-engagers and high-engagers that differed significantly in the …

Evolution Of The Zhx Transcription Factor Family And Analysis Of Zhx2 Target Genes Cyp2a4 And Cyp2a5 In Mouse Liver, Alexandra Nichole Nail

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

The liver is the largest internal organ and performs a wide variety of functions to maintain organismal homeostasis. While some liver functions are carried out by all hepatocytes, other functions are restricted to certain populations of hepatocytes within the liver. This phenomenon, called zonal gene regulation or liver zonation, controls may metabolic processes within the liver including ammonia detoxification; glucose homeostasis; bile acid and glutamine synthesis; and metabolism of xenobiotics, lipids, and amino acids. The liver also expresses many genes in a developmental or sex-biased manner. Some genes are expressed at higher levels early or late in development, or alternatively, …

Examining The Effect Of Socioeconomic Factors On Kindergarten Vaccination Rates In Kentucky Counties, Abigail Wiggins

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

The purpose of this project is to examine the relationship between county-level socioeconomic factors and immunization compliance rates among kindergarten age children. All 120 counties in Kentucky were included in this evaluation.

County-level percent of uninsured children, number of children in poverty, children receiving free lunch (percentage), unemployment rate (percentage), and high school graduation rate were assessed. Socioeconomic data for each county were compared to county-level kindergarten vaccination rates. All vaccination data were obtained from the 2015-2016 Kentucky Annual School Immunization Survey Report. All socioeconomic county data were obtained from the 2016 County Health Rankings data, published by the Robert …