Digital Commons Network^™

Imatinib Mesylate Effects On Zebrafish Reproductive Success: Gonadal Development, Gamete Quality, Fertility, Embryo-Larvae Viability And Development, And Related Genes, Nader Ahmadi, Seyed-Mohammadreza Samaee, Robert A. Yokel, Aliasghar Tehrani

Pharmaceutical Sciences Faculty Publications

Imatinib (IM) is a tyrosine kinase (TK) inhibitor (TKI) used to treat chronic myeloid leukemia. Clinical case reports and a few laboratory mammal studies provide inconclusive evidence about its deleterious effects on reproduction. The aim of the current study was to evaluate the potential of zebrafish to characterize IM-induced effects on reproduction and clarify IM effects on reproductive success. To this end, we exposed adult zebrafish to four concentrations of IM for 30 days followed by a 30-day depuration period. IM exposure caused a concentration-dependent, irreversible, suppression of folliculogenesis, reversible decrease in sperm density and motility, decreased fecundity and fertility, …

Altered Gating Of KV1.4 In The Nucleus Accumbens Suppresses Motivation For Reward, Bernadette O'Donovan, Adewale Adeluyi, Erin L Anderson, Robert D. Cole, Jill R. Turner, Pavel I. Ortinski

Neuroscience Faculty Publications

Deficient motivation contributes to numerous psychiatric disorders, including withdrawal from drug use, depression, schizophrenia, and others. Nucleus accumbens (NAc) has been implicated in motivated behavior, but it remains unclear whether motivational drive is linked to discrete neurobiological mechanisms within the NAc. To examine this, we profiled cohorts of Sprague-Dawley rats in a test of motivation to consume sucrose. We found that substantial variability in willingness to exert effort for reward was not associated with operant responding under low-effort conditions or stress levels. Instead, effort-based motivation was mirrored by a divergent NAc shell transcriptome with differential regulation at potassium and dopamine …

Forage News [2019-09], Department Of Plant And Soil Sciences, University Of Kentucky

Forage News

• Heart of America Grazing Conference
• Register now for Fall Grazing School, Sept. 10-11 in Versailles, KY
• Blue-green Algae: Dangerous to Pets and Livestock
• 12 Habits of Highly Successful Forage Producers
• Cover Crops Following Corn Silage
• Current USDA Hay Market Prices
• Alfalfa Checkoff Funds Two University of Kentucky Projects
• Watch for Fall Army Work in Pastures

Beautiful Connector: Collection Showcase Exhibits As Teaching Tools And Community Builders, Antje Mays

Library Faculty and Staff Publications

Libraries’ quest to strengthen connections with their constituencies often finds expression in new services and repurposed user spaces. Some literature portrays libraries as focusing away from collections toward new trends in library portfolios, but showcasing collections can prove very effective in bringing the library and user communities closer together. This article recounts two recent library collection showcase exhibits as successful examples of bolstering stakeholder connections: The first collections exhibit showcased books on Chinese language, literature, culture, art and architecture, history, and medicine received through the Window of Shanghai program. The second collections exhibit showcased scholarly books, U.S. government publications, citizen …

Investigation Of The Accuracy Of Alcohol And Drug Involvement Reporting, William Nicholas Staats

Kentucky Transportation Center Research Report

Executive Summary

Researchers compared the 2013 to 2017 fatal crash data from the KSP database to the crash data from the FARS database to check the consistency and accuracy of alcohol and drug involvement reporting for drivers in the KSP database. The indications of alcohol and drug involvement in the FARS database were used as the ground truth due to the inclusion of laboratory test results confirming the presence of alcohol and/or drugs in a driver’s system. For the five-year study period, the indications for alcohol involvement were 85.8% consistent and the indications of drug involvement were 66.2% consistent between …

Diabetes-Related Amylin Dyshomeostasis: A Contributing Factor To Cerebrovascular Pathology And Dementia, Han Ly, Florin Despa

Pharmacology and Nutritional Sciences Faculty Publications

Type 2 diabetes (T2D) increases the risk for cerebrovascular disease (CVD) and dementia. The underlying molecular mechanisms remain elusive, which hampers the development of treatment or/and effective prevention strategies. Recent studies suggest that dyshomeostasis of amylin, a satiety hormone that forms pancreatic amyloid in patients with T2D, promotes accumulation of amylin in cerebral small blood vessels and interaction with Alzheimer's disease (AD) pathology. Overexpression of human amylin in rodents (rodent amylin does not form amyloid) leads to late-life onset T2D and neurologic deficits. In this Review, we discuss clinical evidence of amylin pathology in CVD and AD and identify critical …

Flecainide Toxicity Resulting In Pacemaker Latency And Intermittent Failure To Capture, John M. Suffredini, Joshua Rutland, Peter Akpunonu, Regan Baum, John Catanzaro, Claude S. Elayi

Emergency Medicine Faculty Publications

BACKGROUND Flecainide is a class Ic antiarrhythmic agent used in the treatment of supraventricular and ventricular arrhythmias. It is associated with a potent adverse effect profile; however, the effects of flecainide toxicity in the setting of a pacemaker have not been well described. We describe a unique case of flecainide toxicity secondary to acute kidney injury in the setting of a dual-chamber pacemaker, resulting in ventricular capture latency and intermittent failure to capture.

CASE REPORT The patient was a 91-year-old female with a history of atrial fibrillation maintained in sinus rhythm on flecainide, who presented complaining of purple visual disturbances …

Alteration Of Tobacco Alkaloid Content Through Modification Of Specific Cytochrome P450 Genes, Ralph E. Dewey, Balazs Siminszky, Steven W. Bowen, Lily Gavilano

Plant and Soil Sciences Faculty Patents

Compositions and methods for reducing the level of nornicotine and N'-nitrosonomicotine (NNN) in Nicotiana plants and plant parts thereof are provided. The compositions comprise isolated polynucleotides and polypeptides for cytochrome P450s that are involved in the metabolic conversion of nicotine to nornicotine in these plants. Expression cassettes, vectors, plants, and plant parts thereof comprising inhibitory sequences that target expression or function of the disclosed cytochrome P450 polypeptides are also provided. Methods for the use of these novel sequences to inhibit expression or function of cytochrome P450 polypeptides involved in this metabolic conversion are also provided. The methods find use in …

N-Glycosylation-Defective Splice Variants Of Neuropilin-1 Promote Metastasis By Activating Endosomal Signals, Xiuping Huang, Qing Ye, Min Chen, Aimin Li, Wenting Mi, Yuxin Fang, Yekaterina Y. Zaytseva, Kathleen L. O'Connor, Craig W. Vander Kooi, Side Liu, Qing-Bai She

Markey Cancer Center Faculty Publications

Neuropilin-1 (NRP1) is an essential transmembrane receptor with a variety of cellular functions. Here, we identify two human NRP1 splice variants resulting from the skipping of exon 4 and 5, respectively, in colorectal cancer (CRC). Both NRP1 variants exhibit increased endocytosis/recycling activity and decreased levels of degradation, leading to accumulation on endosomes. This increased endocytic trafficking of the two NRP1 variants, upon HGF stimulation, is due to loss of N-glycosylation at the Asn150 or Asn261 site, respectively. Moreover, these NRP1 variants enhance interactions with the Met and β1-integrin receptors, resulting in Met/β1-integrin co-internalization and co-accumulation on endosomes. This provides persistent …

Advances In Gene Ontology Utilization Improve Statistical Power Of Annotation Enrichment, Eugene Waverly Hinderer Iii, Robert M. Flight, Rashmi Dubey, James N. Macleod, Hunter N. B. Moseley

Maxwell H. Gluck Equine Research Center Faculty Publications

Gene-annotation enrichment is a common method for utilizing ontology-based annotations in gene and gene-product centric knowledgebases. Effective utilization of these annotations requires inferring semantic linkages by tracing paths through edges in the ontological graph, referred to as relations. However, some relations are semantically problematic with respect to scope, necessitating their omission or modification lest erroneous term mappings occur. To address these issues, we created the Gene Ontology Categorization Suite, or GOcats—a novel tool that organizes the Gene Ontology into subgraphs representing user-defined concepts, while ensuring that all appropriate relations are congruent with respect to scoping semantics. Here, we demonstrate the …

Imaging Of Glucose Metabolism By 13c-Mri Distinguishes Pancreatic Cancer Subtypes In Mice, Shun Kishimoto, Jeffrey R. Brender, Daniel R. Crooks, Shingo Matsumoto, Tomohiro Seki, Nobu Oshima, Hellmut Merkle, Penghui Lin, Galen Reed, Albert P. Chen, Jan Henrik Ardenkjaer-Larsen, Jeeva Munasinghe, Keita Saito, Kazutoshi Yamamoto, Peter L. Choyke, James Mitchell, Andrew N. Lane, Teresa W. M. Fan, W. Marston Linehan, Murali C. Krishna

Center for Environmental and Systems Biochemistry Faculty Publications

Metabolic differences among and within tumors can be an important determinant in cancer treatment outcome. However, methods for determining these differences non-invasively in vivo is lacking. Using pancreatic ductal adenocarcinoma as a model, we demonstrate that tumor xenografts with a similar genetic background can be distinguished by their differing rates of the metabolism of 13C labeled glucose tracers, which can be imaged without hyperpolarization by using newly developed techniques for noise suppression. Using this method, cancer subtypes that appeared to have similar metabolic profiles based on steady state metabolic measurement can be distinguished from each other. The metabolic maps from …

Rna-Based Compositions And Adjuvants For Prophylactic And Therapeutic Treatment, Peixuan Guo, Hui Li, Emil F. Khisamutdinov, Daniel L. Jasinski

Pharmaceutical Sciences Faculty Patents

The present invention is directed towards an artificial RNA nano structure comprising multiple external strands of RNA, each external strand comprising about 40-50 nucleotides; one internal strand of RNA comprising more than about 50 nucleotides; the internal strands and external strands assembled to form a triangle nanostructure, a square nanostructure, or a polygon nanostructure and a pRNA three-way junction (3WJ) motif at each vertex of the nanostructure. Such nanostructure can be provided in a composition together with an adjuvant for use in inducing the production of high affinity neutralizing antibodies or inhibitory antibodies, inducing the production of cytokines, inducing an …

The Effects Of Aging On Sleep Parameters In A Healthy, Melatonin-Competent Mouse Model, Jiffin K. Paulose, Chanung Wang, Bruce F. O'Hara, Vincent M. Cassone

Biology Faculty Publications

Background: Sleep disturbances are common maladies associated with human age. Sleep duration is decreased, sleep fragmentation is increased, and the timing of sleep onset and sleep offset is earlier. These disturbances have been associated with several neurodegenerative diseases. Mouse models for human sleep disturbances can be powerful due to the accessibility to neuroscientific and genetic approaches, but these are hampered by the fact that most mouse models employed in sleep research have spontaneous mutations in the biosynthetic pathway(s) regulating the rhythmic production of the pineal hormone melatonin, which has been implicated in human sleep.

Purpose and method: The present study …

Forage News [2019-08], Department Of Plant And Soil Sciences, University Of Kentucky

Forage News

• Reclaiming Rundown Farms - Western KY Summer Forage Tour
• Oats for Fall Pasture or Hay
• KFGC Central KY Field Day
• The Birth of a Rotational Grazing System
• Caldwell County Horse Farm to Host Field Day

Equine Arteritis Virus Long-Term Persistence Is Orchestrated By Cd8+ T Lymphocyte Transcription Factors, Inhibitory Receptors, And The Cxcl16/Cxcr6 Axis, Mariano Carossino, Pouya Dini, Theodore S. Kalbfleisch, Alan T. Loynachan, Igor F. Canisso, R. Frank Cook, Peter J. Timoney, Udeni B. R. Balasuriya

Veterinary Science Faculty Publications

Equine arteritis virus (EAV) has the unique ability to establish long-term persistent infection in the reproductive tract of stallions and be sexually transmitted. Previous studies showed that long-term persistent infection is associated with a specific allele of the CXCL16 gene (CXCL16S) and that persistence is maintained despite the presence of local inflammatory and humoral and mucosal antibody responses. Here, we performed transcriptomic analysis of the ampullae, the primary site of EAV persistence in long-term EAV carrier stallions, to understand the molecular signatures of viral persistence. We demonstrated that the local CD8⁺ T lymphocyte response is predominantly orchestrated …

Targeting Pathogenic Lafora Bodies In Lafora Disease Using An Antibody-Enzyme Fusion, M. Kathryn Brewer, Annette M. Uittenbogaard, Grant L. Austin, Dyann M. Segvich, Anna Depaoli-Roach, Peter J. Roach, John J. Mccarthy, Zoe R. Simmons, Jason A. Brandon, Zhengqiu Zhou, Jill Zeller, Lyndsay E. A. Young, Ramon C. Sun, James R. Pauly, Nadine M. Aziz, Bradley L. Hodges, Tracy R. Mcknight, Dustin D. Armstrong, Matthew S. Gentry

Molecular and Cellular Biochemistry Faculty Publications

Lafora disease (LD) is a fatal childhood epilepsy caused by recessive mutations in either the EPM2A or EPM2B gene. A hallmark of LD is the intracellular accumulation of insoluble polysaccharide deposits known as Lafora bodies (LBs) in the brain and other tissues. In LD mouse models, genetic reduction of glycogen synthesis eliminates LB formation and rescues the neurological phenotype. Therefore, LBs have become a therapeutic target for ameliorating LD. Herein, we demonstrate that human pancreatic α-amylase degrades LBs. We fused this amylase to a cell-penetrating antibody fragment, and this antibody-enzyme fusion (VAL-0417) degrades LBs in vitro and dramatically reduces LB …

White Matter Hyperintensity Regression: Comparison Of Brain Atrophy And Cognitive Profiles With Progression And Stable Groups, Omar M. Al-Janabi, Christopher E. Bauer, Larry B. Goldstein, Richard R. Murphy, Ahmed A. Bahrani, Charles D. Smith, Donna M. Wilcock, Brian T. Gold, Gregory A. Jicha

Sanders-Brown Center on Aging Faculty Publications

Subcortical white matter hyperintensities (WMHs) in the aging population frequently represent vascular injury that may lead to cognitive impairment. WMH progression is well described, but the factors underlying WMH regression remain poorly understood. A sample of 351 participants from the Alzheimer’s Disease Neuroimaging Initiative 2 (ADNI2) was explored who had WMH volumetric quantification, structural brain measures, and cognitive measures (memory and executive function) at baseline and after approximately 2 years. Selected participants were categorized into three groups based on WMH change over time, including those that demonstrated regression (n = 96; 25.5%), stability (n = 72; 19.1%), and …

Dialectical Methods And The Stoicheia Paradigm In Plato’S Trilogy And Philebus, Colin C. Smith

Philosophy Graduate Research

Plato’s Theaetetus, Sophist, and Statesman exhibit several related dialectical methods relevant to Platonic education: maieutic in Theaetetus, bifurcatory division in Sophist and Statesman, and non-bifurcatory division in Statesman, related to the ‘god-given’ method in Philebus. I consider the nature of each method through the letter or element (στοιχεῖον) paradigm, used to reflect on each method. At issue are the element’s appearances in given contexts, its fitness for communing with other elements like it in kind, and its own nature defined through its relations to others. These represent stages of inquiry for the Platonic student inquiring into the sources of knowledge.

Ccr3 Inhibition For Ocular Angiogenesis And Macular Degeneration, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Patents

Provided are methods and compositions for the treatment or prevention of ocular angiogenesis and neovascularization. Administration of inhibitors of the CCR3 receptor or its ligands eotaxin (CCL11), eotaxin-2 (CCL24) or eotaxin-3 (CCL26) inhibits ocular angiogenesis.

Beneficial Reuse Of Industrial Co2 Emissions Using A Microalgae Photobioreactor: Waste Heat Utilization Assessment, Daniel T. Mohler, Michael H. Wilson, Zhen Fan, John G. Groppo, Mark Crocker

Center for Applied Energy Research Faculty and Staff Publications

Microalgae are a potential means of recycling CO₂ from industrial point sources. With this in mind, a novel photobioreactor (PBR) was designed and deployed at a coal-fired power plant. To ascertain the feasibility of using waste heat from the power plant to heat algae cultures during cold periods, two heat transfer models were constructed to quantify PBR cooling times. The first, which was based on tabulated data, material properties and the physical orientation of the PBR tubes, yielded a range of heat transfer coefficients of 19–64 W m⁻² K⁻¹ for the PBR at wind speeds of 1–10 …

The Social Documentary Photography Of Milton Rogovin, Christopher Fulton

Civil Rights

Milton Rogovin (1909–2011) dedicated his photographic career to capturing the humanity of working-class people around the world—coal miners, factory workers, the urban poor, the residents of Appalachia, and other marginalized groups. He worked to equalize the relationship between photographer and subject in the making of pictures and encouraged his subjects' agency by photographing them on their own terms. Rogovin's powerful insight and immense sympathy for his subjects distinguish him as one of the most original and important documentary photographers in American history.

Edited by Christopher Fulton, The Social Documentary Photography of Milton Rogovin is a multi-disciplinary study of the photographer's …

Neurocognitive Basis Of Repetition Deficits In Primary Progressive Aphasia, Sladjana Lukic, Maria Luisa Mandelli, Ariane Welch, Kesshi Jordan, Wendy Shwe, John Neuhaus, Zachary Miller, H. Isabel Hubbard, Maya Henry, Bruce L. Miller, Nina F. Dronkers, Maria Luisa Gorno-Tempini

Communication Sciences and Disorders Faculty Publications

Previous studies indicate that repetition is affected in primary progressive aphasia (PPA), particularly in the logopenic variant, due to limited auditory-verbal short-term memory (avSTM). We tested repetition of phrases varied by length (short, long) and meaning (meaningful, non-meaningful) in 58 participants (22 logopenic, 19 nonfluent, and 17 semantic variants) and 21 healthy controls using a modified Bayles repetition test. We evaluated the relation between cortical thickness and repetition performance and whether sub-scores could discriminate PPA variants.

Logopenic participants showed impaired repetition across all phrases, specifically in repeating long phrases and any phrases that were non-meaningful. Nonfluent, semantic, and healthy control …

Forage News [2019-07], Department Of Plant And Soil Sciences, University Of Kentucky

Forage News

• Register for Heart of America and Western Kentucky Grazing Conferences today!
• The Clover Dilemma
• Improve Summer Pastures with Crabgrass
• Fall Grazing School Registration Now Open
• Clip Pastures to Reduce the Risk of Ergot

Southeastern Law Librarian Summer 2019, Seaall

Newsletters

No abstract provided.

Phospholipases D: Making Sense Of Redundancy And Duplication, Andrew J. Morris

Internal Medicine Faculty Publications

Why have two genes when one would suffice? Evolutionary pressure means that biology, unlike government, is generally intolerant of wasted effort. Therefore, when multiple genes exist presumably they are there to provide some benefit to the organism even if that benefit is not immediately obvious to us scientists. A recent report from Raghu and colleagues (Biosci. Rep. (2018) 38, pii: BSR20181690) [1] sheds some light on one possible reason for the existence of two Phospholipases D genes in chordates when only one is present in invertebrates.

Modulation Of Osteogenic And Myogenic Differentiation By A Phytoestrogen Formononetin Via P38mapk-Dependent Jak-Stat And Smad-1/5/8 Signaling Pathways In Mouse Myogenic Progenitor Cells, Ilavenil Soundharrajan, Da Hye Kim, Palaniselvam Kuppusamy, Ki Choon Choi

Center for Research on Environmental Disease Faculty Publications

Formononetin (FN), a typical phytoestrogen has attracted substantial attention as a novel agent because of its diverse biological activities including, osteogenic differentiation. However, the molecular mechanisms underlying osteogenic and myogenic differentiation by FN in C2C12 progenitor cells remain unknown. Therefore the objective of the current study was to investigate the action of FN on myogenic and osteogenic differentiation and its impact on signaling pathways in C2C12 cells. FN significantly increased myogenic markers such as Myogenin, myosin heavy chains, and myogenic differentiation 1 (MyoD). In addition, the expression of osteogenic specific genes alkaline phosphatase (ALP), Run-related transcription factor 2(RUNX2), and osteocalcin …

Prognostic Role Of Elevated Myeloperoxidase In Patients With Acute Coronary Syndrome: A Systemic Review And Meta-Analysis, Andrew R. Kolodziej, Mohamed Abo-Aly, Eman Elsawalhy, Charles Campbell, Khaled M. Ziada, Ahmed K. Abdel-Latif

Gill Heart & Vascular Institute Faculty Publications

Background. Myocardial inflammation following acute ischemic injury has been linked to poor cardiac remodeling and heart failure. Many studies have linked myeloperoxidase (MPO), a neutrophil and inflammatory marker, to cardiac inflammation in the setting of acute coronary syndrome (ACS). However, the prognostic role of MPO for adverse clinical outcomes in ACS patients has not been well established. Methods. MEDLINE and Cochrane databases were searched for studies from 1975 to March 2018 that investigated the prognostic value of serum MPO in ACS patients. Studies which have dichotomized patients into a high MPO group and a low MPO group reported clinical outcomes …

Climate Change Impacts On Winter Wheat Yield In Northern China, Xiu Geng, Fang Wang, Wei Ren, Zhixin Hao

Plant and Soil Sciences Faculty Publications

Exploring the impacts of climate change on agriculture is one of important topics with respect to climate change. We quantitatively examined the impacts of climate change on winter wheat yield in Northern China using the Cobb–Douglas production function. Utilizing time-series data of agricultural production and meteorological observations from 1981 to 2016, the impacts of climatic factors on wheat production were assessed. It was found that the contribution of climatic factors to winter wheat yield per unit area (WYPA) was 0.762–1.921% in absolute terms. Growing season average temperature (GSAT) had a negative impact on WYPA for the period of 1981–2016. A …

¿Poder Del Discurso O Discurso De Poder? La Representación De Los Migrantes Ecuatorianos En La Utopía De Madrid, Francesco Masala

Nomenclatura: aproximaciones a los estudios hispánicos

After enduring a decade of economic, climatic, and political problems, between 1999 and 2006, more than 900,000 Ecuadorians left their country (INEC 2007). This process marked the beginning of a major migratory movement which has caused Spain to become a premier destination. The response to such migration has been disparate, yet both Ecuadorian and Spanish artists (as well as the Spanish press) have shown the different perspectives related to a discriminatory ideology. This article focuses on the representation of Ecuadorians in Spain in the 21st century. Despite the large production of novels related to this topic, the one that best …

Xx Sex Chromosome Complement Promotes Atherosclerosis In Mice, Yasir Alsiraj, Xuqi Chen, Sean E. Thatcher, Ryan E. Temel, Lei Cai, Eric M. Blalock, Wendy Katz, Heba M. Ali, Michael C. Petriello, Pan Deng, Andrew J. Morris, Xuping Wang, Aldons J. Lusis, Arthur P. Arnold, Karen Reue, Katherine L. Thompson, Patrick Tso, Lisa A. Cassis

Pharmacology and Nutritional Sciences Faculty Publications

Men and women differ in circulating lipids and coronary artery disease (CAD). While sex hormones such as estrogens decrease CAD risk, hormone replacement therapy increases risk. Biological sex is determined by sex hormones and chromosomes, but effects of sex chromosomes on circulating lipids and atherosclerosis are unknown. Here, we use mouse models to separate effects of sex chromosomes and hormones on atherosclerosis, circulating lipids and intestinal fat metabolism. We assess atherosclerosis in multiple models and experimental paradigms that distinguish effects of sex chromosomes, and male or female gonads. Pro-atherogenic lipids and atherosclerosis are greater in XX than XY mice, indicating …