Digital Commons Network^™

Diaphragm Abnormalities In Patients With End-Stage Heart Failure: Nadph Oxidase Upregulation And Protein Oxidation, Bumsoo Ahn, Philip D. Coblentz, Adam W. Beharry, Nikhil Patel, Andrew R. Judge, Jennifer S. Moylan, Charles W. Hoopes, Mark R. Bonnell, Leonardo F. Ferreira

Physiology Faculty Publications

Patients with heart failure (HF) have diaphragm abnormalities that contribute to disease morbidity and mortality. Studies in animals suggest that reactive oxygen species (ROS) cause diaphragm abnormalities in HF. However, the effects of HF on ROS sources, antioxidant enzymes, and protein oxidation in the diaphragm of humans is unknown. NAD(P)H oxidase, especially the Nox2 isoform, is an important source of ROS in the diaphragm. Our main hypothesis was that diaphragm from patients with HF have heightened Nox2 expression and p47^phox phosphorylation (marker of enzyme activation) that is associated with elevated protein oxidation. We collected diaphragm biopsies from patients with …

Functional And Structural Studies On The Neisseria Gonorrhoeae Gmha, The First Enzyme In The Glycero-Manno-Heptose Biosynthesis Pathways, Demonstrate A Critical Role In Lipooligosaccharide Synthesis And Gonococcal Viability, Igor H. Wierzbicki, Ryszard A. Zielke, Konstantin V. Korotkov, Aleksandra E. Sikora

Molecular and Cellular Biochemistry Faculty Publications

Sedoheptulose-7-phosphate isomerase, GmhA, is the first enzyme in the biosynthesis of nucleotide-activated-glycero-manno-heptoses and an attractive, yet underexploited, target for development of broad-spectrum antibiotics. We demonstrated that GmhA homologs in Neisseria gonorrhoeae and N. meningitidis (hereafter called GmhA_GC and GmhA_NM, respectively) were interchangeable proteins essential for lipooligosaccharide (LOS) synthesis, and their depletion had adverse effects on neisserial viability. In contrast, the Escherichia coli ortholog failed to complement GmhA_GC depletion. Furthermore, we showed that GmhA_GC is a cytoplasmic enzyme with induced expression at mid-logarithmic phase, upon iron deprivation and anaerobiosis, and conserved in contemporary gonococcal …

Predictive Screening Of M1 And M2 Macrophages Reveals The Immunomodulatory Effectiveness Of Post Spinal Cord Injury Azithromycin Treatment, John C. Gensel, Timothy J. Kopper, Bei Zhang, Michael B. Orr, William M. Bailey

Spinal Cord and Brain Injury Research Center Faculty Publications

Spinal cord injury (SCI) triggers a heterogeneous macrophage response that when experimentally polarized toward alternative forms of activation (M2 macrophages) promotes tissue and functional recovery. There are limited pharmacological therapies that can drive this reparative inflammatory state. In the current study, we used in vitrosystems to comprehensively defined markers of macrophages with known pathological (M1) and reparative (M2) properties in SCI. We then used these markers to objectively define the macrophage activation states after SCI in response to delayed azithromycin treatment. Mice were subjected to moderate-severe thoracic contusion SCI. Azithromycin or vehicle was administered beginning 30 minutes post-SCI and …

Genome Editing Of Wnt-1, A Gene Associated With Segmentation, Via Crispr/Cas9 In The Pine Caterpillar Moth, Dendrolimus Punctatus, Huihui Liu, Qun Liu, Xuguo Zhou, Yongping Huang, Zhen Zhang

Entomology Faculty Publications

The pine caterpillar moth, Dendrolimus punctatus, is a devastating forest pest. Genetic manipulation of this insect pest is limited due to the lack of genomic and functional genomic toolsets. Recently, CRISPR/Cas9 technology has been demonstrated to be a promising approach to modify the genome. To investigate gene functions during the embryogenesis, we introduced CRISPR/Cas9 system in D. punctatus to precisely and effectively manipulate gene expressions inmutant embryos. Compared to controls, knocking out of DpWnt-1, a gene well known for its role in the early body planning, led to high embryonic mortality. Among these mutants, 32.9% of the embryos …

Myogenic Progenitor Cells Control Extracellular Matrix Production By Fibroblasts During Skeletal Muscle Hypertrophy, Christopher S. Fry, Tyler J. Kirby, Kate Kosmac, John J. Mccarthy, Charlotte A. Peterson

Physiology Faculty Publications

Satellite cells, the predominant stem cell population in adult skeletal muscle, are activated in response to hypertrophic stimuli and give rise to myogenic progenitor cells (MPCs) within the extracellular matrix (ECM) that surrounds myofibers. This ECM is composed largely of collagens secreted by interstitial fibrogenic cells, which influence satellite cell activity and muscle repair during hypertrophy and aging. Here we show that MPCs interact with interstitial fibrogenic cells to ensure proper ECM deposition and optimal muscle remodeling in response to hypertrophic stimuli. MPC-dependent ECM remodeling during the first week of a growth stimulus is sufficient to ensure long-term myofiber hypertrophy. …

Inhibition Of Mammalian Glycoprotein Ykl-40 Identification Of The Physiological Ligand, Abhishek A. Kognole, Christina M. Payne

Chemical and Materials Engineering Faculty Publications

YKL-40 is a mammalian glycoprotein associated with progression, severity, and prognosis of chronic inflammatory diseases and a multitude of cancers. Despite this well documented association, identification of the lectin′s physiological ligand and, accordingly, biological function has proven experimentally difficult. YKL-40 has been shown to bind chito-oligosaccharides; however, the production of chitin by the human body has not yet been documented. Possible alternative ligands include proteoglycans, polysaccharides, and fibers like collagen, all of which makeup the extracellular matrix. It is likely that YKL-40 is interacting with these alternative polysaccharides or proteins within the body, extending its function to cell biological roles …

Sesquiterpene Synthase Gene And Protein, Joseph Chappell, Bryan T. Greenhagen

Pharmaceutical Sciences Faculty Patents

The invention relates to sesquiterpene synthases and methods for their production and use. Particularly, the invention provides nucleic acids comprising the nucleotide sequence of citrus valencene synthase (CVS) which codes for at least one CVS. The invention further provides nucleic acids comprising the nucleotide sequence coding for amino acid residues forming the tier 1 and tier 2 domains of CVS. The invention also provides for methods of making and using the nucleic acids and amino acids of the current invention.

Three-Dimensional Imaging Of The Intracellular Assembly Of A Functional Viral Rna Replicase Complex, Isabel Fernández De Castro, José J. Fernández, Daniel Barajas, Peter D. Nagy, Cristina Risco

Plant Pathology Faculty Publications

Positive-strand RNA viruses, which can be devastating pathogens in humans, animals and plants, replicate their genomes on intracellular membranes. Here, we describe the three-dimensional ultrastructural organization of a tombusvirus replicase in yeast, a valuable model for exploring virus–host interactions. We visualized the intracellular distribution of a viral replicase protein using metal-tagging transmission electron microscopy, a highly sensitive nanotechnology whose full potential remains to be developed. These three-dimensional images show how viral replicase molecules are organized when they are incorporated into the active domains of the intracellular replication compartment. Our approach provides a means to study protein activation mechanisms in cells …

The Family Rhabdoviridae: Mono- And Bipartite Negative-Sense Rna Viruses With Diverse Genome Organization And Common Evolutionary Origins, Ralf G. Dietzgen, Hideki Kondo, Michael M. Goodin, Gael Kurath, Nikos Vasilakis

Plant Pathology Faculty Publications

The family Rhabdoviridae consists of mostly enveloped, bullet-shaped or bacilliform viruses with a negative-sense, single-stranded RNA genome that infect vertebrates, invertebrates or plants. This ecological diversity is reflected by the diversity and complexity of their genomes. Five canonical structural protein genes are conserved in all rhabdoviruses, but may be overprinted, overlapped or interspersed with several novel and diverse accessory genes. This review gives an overview of the characteristics and diversity of rhabdoviruses, their taxonomic classification, replication mechanism, properties of classical rhabdoviruses such as rabies virus and rhabdoviruses with complex genomes, rhabdoviruses infecting aquatic species, and plant rhabdoviruses with both mono- …

Increased Ros Production In Non-Polarized Mammary Epithelial Cells Induces Monocyte Infiltration In 3d Culture, Linzhang Li, Jie Chen, Gaofeng Xiong, Daret K. St. Clair, Wei Xu, Ren Xu

Markey Cancer Center Faculty Publications

Loss of epithelial cell polarity promotes cell invasion and cancer dissemination. Therefore, identification of factors that disrupt polarized acinar formation is crucial. Reactive oxygen species (ROS) drive cancer progression and promote inflammation. Here, we show that the non-polarized breast cancer cell line T4-2 generates significantly higher ROS levels than polarized S1 and T4R cells in three-dimensional (3D) culture, accompanied by induction of the nuclear factor κB (NF-κB) pathway and cytokine expression. Minimizing ROS in T4-2 cells with antioxidants reestablished basal polarity and inhibited cell proliferation. Introducing constitutively activated RAC1 disrupted cell polarity and increased ROS levels, indicating that RAC1 is …

Three Essays On Food Safety Regulations And International Trade Of Agricultural Products, Jun Ho Seok

Theses and Dissertations--Agricultural Economics

This dissertation investigates food safety regulations and international trade of agricultural products dividing into three aspects: the signalling effect from U.S. strict food safety regulations on U.S. vegetable exports, political determinants of sanitary and photosanitary non-tariff barriers, and the impact of trade barriers on employment in developing countries. In chapter 2, we investigate the impact of high U.S. maximum residue limit (MRL) standards on U.S vegetable exports to 102 countries utilizing the hierarchical model. MRL, which is one of non-tariff barriers with respect to food safety, is applied to home and foreign countries at the same time. Thus, firms in …

It's Time: A Meta-Analysis On The Self-Control-Deviance Link, Alexander T. Vazsonyi, Jakub Mikuška, Erin L. Kelley

Family Sciences Faculty Publications

Purpose
The current meta-analysis examines the link between self-control and measures of crime and deviance, taking stock of the empirical status of self-control theory and focusing on work published between 2000 and 2010.

Methods
A total of 796 studies were reviewed for inclusion/exclusion criteria and yielded a final study sample of 99 studies (88 cross-sectional and 19 longitudinal effect sizes, analyzed separately). Random effects mean correlations between self-control and deviance were analyzed for cross-sectional and longitudinal studies, respectively. Publication bias was assessed using multiple methods.

Results
A random effects mean correlation between self-control and deviance was M_r = 0.415 …

The School Food Environment And Its Association With Dietary Intake Among Rural Adolescents, Hannah F. Hickey

Theses and Dissertations--Nutrition and Food Systems

The school food environment has the ability to increase the consumption of fruit and vegetables in rural adolescents. This study used a survey to allow adolescents in seven rural counties to self-report their fruit and vegetable intake as well as utilizing the USDA Mathematica tool and the School Nutrition and Meal Cost Study audits to evaluate what food and beverage products were actually available to adolescents. By using these two measures, associations between fruit and vegetable intake and availability of healthy and unhealthy foods were determined. The availability of healthy snacks and beverages was found to be associated with sugar-sweetened …

Human Rights: From Legal Transplants To Fair Translation, James M. Donovan

Law Faculty Scholarly Articles

The current regime of international human rights suffers from three shortcomings: First, it has failed to adequately address the reality of cultural diversity. Second, the formalized human rights treaties have been ineffective in their ability to compel states to reform their behaviors, and third, the uncontrolled growth in the number of human rights weakens the impact of appeals to that standard.

Although treated as independent problems, this paper finds that these three limitations are sufficiently linked such that a remedy to the first will simultaneously resolve the others. Parts I and II of the paper describe how the imposition of …

Immune Evasion By Division Of Labor: The Trophic Life Cycle Stage Of Pneumocystis Murina Suppresses Innate Immunity To This Opportunistic, Fungal Pathogen, Heather M. Evans

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

Pneumocystis species are opportunistic fungal pathogens that cause severe pneumonia in immunocompromised hosts, including AIDS patients. Pneumocystis species have a biphasic life cycle consisting of single-nucleated trophic forms and ascus-like cysts. Both stages live within the host, and, thus, must contend with threats from the host immune system. The cyst cell wall β-glucans have been shown to stimulate immune responses in lung epithelial cells, dendritic cells and alveolar macrophages. Little is known about how the trophic life forms, which do not have a fungal cell wall, interact with immune cells. In this study, the immune response to the life cycle …

Antisense Afp Transcripts In Mouse Liver And Their Potential Role In Afp Gene Regulation, Maria S. Dixon

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

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, ranking the sixth most common cancer and third most common cause of cancer mortality worldwide. Alpha-fetoprotein (AFP) is a plasma protein that is highly expressed in the fetal liver and shut off after birth. AFP expression is elevated in regenerating adult liver and HCC and has been used extensively as a diagnostic marker of liver cancer. We have been studying mouse liver gene regulation to better understand mechanisms by which changes in gene expression contribute to liver development, homeostasis and disease. Zinc Fingers and Homeoboxes 2 (Zhx2) has …

Therapeutic Potential Of Targeting Reactive Oxygen Species (Ros) Stress In Myelodysplastic Syndrome (Mds), Karine Z. Oben

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

Myelodysplastic syndromes (MDS) are a diverse group of clonal hematologic disorders characterized by ineffective blood cell production (hematopoiesis), dysplastic (abnormal) cell morphology in one or more hematopoietic lineages, and progression to acute myeloid leukemia (AML). The response rate to current FDA approved therapies is low and not durable. Just about 50% of MDS patients respond to these drug therapies and a majority of responders relapse within 2-3 years. Hence there is a compelling need to investigate new therapy options.

We investigated the anticancer potential and possible underlying molecular mechanisms of action of a plant-derived compound, Withaferin A (WFA) in MDS. …

Sociodemographic And Clinical Predictors Of Triple Negative Breast Cancer, Madison Ries

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

Background and Objectives

Breast cancer has the highest incidence rates among women and is the second leading cause of death due to cancer in women. Of all breast cancers, triple negative breast cancer (TNBC) accounts for about one-fifth of breast cancer and tends to result in an aggressive form with larger tumors and rates of metastasis and is more frequently found in younger women. This results in an important need in information regarding the risk of diagnosis with triple negative breast cancer over other forms and covariates associated with death and TNBC. This paper studies the relationship between race, tobacco …

Parental Empathy, Aggressive Parenting And Child Adjustment In A High Risk Sample, Shuang Bi

Theses and Dissertations--Psychology

The current study examined the relation between parental empathy, parenting aggression and child maladjustment in a group of parents who perpetrated child abuse and neglect. Twenty parents who were court mandated to receive a parenting intervention program at the Nest Center for Women, Children, and Families participated in this research study. Information about parental dispositional empathy, parent-child specific empathy, parenting aggression and child internalizing and externalizing symptoms were collected through an interview with the parents. Parents in this study reported high levels of dispositional empathy, but exhibited low to moderate levels of empathy in a parent-child relationship rated by coders. …

Examining Racism And White Allyship Among Counseling Psychologists, Kathryn H. Owen

Theses and Dissertations--Educational, School, and Counseling Psychology

Historically, research has focused on White individuals’ initial responses to learning about White privilege and other indicators of early stages of racial awareness and identity development. However, the literature is relatively sparse regarding understanding the experiences of racial identity development in White individuals who are beyond initial introductions to racial awareness, such as Counseling Psychologists (CPs). The assumption is that Counseling Psychology professionals are adequately trained to provide efficacious mental health services and engage in culturally sensitive work activities; however, research indicates that Black clients, colleagues, and graduate students experience racism, such as microaggressions, when interacting with White CPs.

The …

“I Wonder What You Think Of Me”: A Qualitative Approach To Examining Stereotype Awareness In Appalachian Students, Chelsea G. Adams

Theses and Dissertations--Educational, School, and Counseling Psychology

Historically, Appalachia has been stereotyped as being a culture bred in poverty and ignorance. Much research has shown that stereotyping reveals a pattern of behavioral change and an impact on psychological well-being for the stereotyped (e.g., Pinel, 1999; Woodcock, Jernandez, Estrada, & Schultz, 2012), and has largely been centered on race and gender (e.g., Byrnes, 2008; Tuckman & Monetti, 2011). Less is known about the development of culture-specific stereotypes such as those related to Appalachians – a highly stigmatized group (Daniels, 2014; Otto, 2002). The purpose of this study was to gain an understanding of how adolescents in rural Appalachia …

Disparities In Stage-Appropriate Therapy For Resectable Non-Small Cell Lung Cancer In Kentucky, Jeremiah T. Martin

Theses and Dissertations--Clinical Research Design

Lung cancer (NSCLC) is the leading cause of cancer related mortality. Lung cancer screening aims to detect treatable cancers, however survival advantage will only be seen with early and appropriate stage-directed therapy. This study aims to understand recent rates of therapy for early-stage lung cancer in Kentucky, and to explore potential sources of disparities in treatment and outcomes. A Kentucky Cancer Registry query was performed of all NSCLC cases treated in the state from 2005-2014. Of 39,763 lung cancer patients, 10,622 were clinically operable. Of these, overall 40% did not receive surgery, while 16% did not receive any stage-appropriate local …

Arranged Marriage In Village & Middle Class India, Umang Khandpur

Lewis Honors College Capstone Collection

In order to ensure compatibility and future sustenance of a marriage, most people devote significant time in a preparatory phase known as dating. More time spent dating would sensibly correlate to higher marriage longevities as the partners become more acquainted with the intricacies of each other. Ironically, the countries who practice this Western ideology of marriage harbor staggering divorce-to-marriage ratios (some upwards of 60%) while those with a different concept of marriage e.g. India experience much higher marriage longevities. To illuminate this seeming paradox, multiple sources were consulted including current literature, newspaper columns, economic reports, films, television series, and personal …

The Role Of The Community Capital Framework And Christian Faith-Based Community Development Organizations In Kentucky, Samson S. Tarpeh

Theses and Dissertations--Community & Leadership Development

The purpose of this study is to investigate the work of Christian faith-based organizations (FBO) doing community development work in Kentucky and to learn about how they might be using community development concepts and system approaches as articulated in the Community Capitals Framework (CCF) and to critically examine those findings. The CCF is comprised of seven capitals including Natural, Cultural, Human, Social, Political, Financial, and Built. Emery and Flora (2006) assert that the “CCF offers a way to analyze community and economic development efforts from a systems perspective by identifying the assets in each capital (stock), the types of capital …

Aβ Vaccination In Combination With Behavioral Enrichment In Aged Beagles: Effects On Cognition, Aβ, And Microhemorrhages, Paulina R. Davis, Ginevra Giannini, Karin Rudolph, Nathaniel Calloway, Christopher M. Royer, Tina L. Beckett, M. Paul Murphy, Frederick Bresch, Dieter Pagani, Thomas Platt, Xiaohong Wang, Amy Skinner Donovan, Tiffany L. Sudduth, Wenjie Lou, Erin L. Abner, Richard J. Kryscio, Donna M. Wilcock, Edward G. Barrett, Elizabeth Head

Sanders-Brown Center on Aging Faculty Publications

Beta-amyloid (Aβ) immunotherapy is a promising intervention to slow Alzheimer’s disease (AD). Aging dogs naturally accumulate Aβ and show cognitive decline. An active vaccine against fibrillar Aβ 1–42 (VAC) in aged beagles resulted in maintenance but not improvement of cognition along with reduced brain Aβ. Behavioral enrichment (ENR) led to cognitive benefits but no reduction in Aβ. We hypothesized cognitive outcomes could be improved by combining VAC with ENR in aged dogs. Aged dogs (11–12 years) were placed into 4 groups: (1) control/control (C/C); (2) control/VAC (C/V); (3) ENR/control (E/C); (4) ENR and VAC (E/V) and treated for 20 months. …

Forage News [2017-01], Department Of Plant And Soil Sciences, University Of Kentucky

Forage News

• 2016 Long-Term Summary of Kentucky Forage Variety Trials
• Purchase Improved Clovers for Frost Seeding NOW
• Roundup-Ready Alfalfa Variety Differences
• Understanding and Improving Fermentation in Alfalfa and Grass Baleage

The Cost Of Hope At The End Of Life: An Analysis Of State Right-To-Try Statutes, Tamara J. Patterson

Kentucky Law Journal

No abstract provided.

Actus Reus, Mens Rea, And Brain Science: What Do Volition And Intent Really Mean?, Erica Beecher-Monas, Edgar Garcia-Rill

Kentucky Law Journal

The foundational elements of criminal law, actus reus and mens rea, are vague, imprecise, and indeterminate categories that are based on outdated notions about human behavior. These confused categories affect not only what legally constitutes choice, volition, and intent, but also the defendant's ability to present evidence (since the categories define the evidence that will be admissible), and ultimately, criminal liability. In this Article we explain how neuroscience allows us to reconsider these legal concepts and conceive a more informed view of human behavior (and therefore criminal liabilty). The Article explains how distortions in brain function affect the way …

An Examination Of Milk Quality Effects On Milk Yield And Dairy Production Economics In The Southeastern United States, Derek T. Nolan

Theses and Dissertations--Animal and Food Sciences

Mastitis is one of the most costly diseases to dairy producers around the world with milk yield loss being the biggest contributor to economic losses. The objective of first study of this thesis was to determine the impacts of high somatic cell counts on milk yield loss. To accomplish this, over one million cow data records were collected from Southeastern US dairy herds. The objective of the second study was to determine optimum treatment cost of clinical mastitis by combining two economic modeling approaches used in animal health economics. The last objective of this thesis was to determine how much …

Molecularly Imprinted Polymers Synthesized As Adsorbents For Ergot Alkaloids: Characterization And In Vitro And Ex Vivo Assessment Of Effects On Ergot Alkaloid Bioavailability, Manoj B. Kudupoje

Theses and Dissertations--Animal and Food Sciences

Alkaloid toxicities negatively impact livestock health and production and are of serious economic concern to animal industries. To date, few strategies have been developed to evaluate alkaloid levels in feed or to counteract alkaloid toxicities. The present research evaluated the applicability of imprinting technology to synthesize polymers that have potential to interact with ergot alkaloids and therefore reduce their bioavailability in the GIT. The studies also evaluated applicability of synthesized polymers for use in the ruminal environment using an in vitro ruminal fermentation model, and for the ability to ameliorate vasoconstriction using ex vivo myographic evaluations.

In the first experiment, …