Digital Commons Network^™

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

Plant and Soil 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.

High-Activity Mutants Of Butyrylcholinesterase For Cocaine Hydrolysis And Method Of Generating The Same, Chang-Guo Zhan, Hoon Cho, Hsin-Hsiung Tai

Pharmaceutical Sciences Faculty Patents

A novel computational method and generation of mutant butyrylcholinesterase for cocaine hydrolysis is provided. The method includes molecular modeling a possible BChE mutant and conducting molecular dynamics simulations and hybrid quantum mechanical/molecular mechanical calculations thereby providing a screening method of possible BChE mutants by predicting which mutant will lead to a more stable transition state for a rate determining step. Site-directed mutagenesis, protein expression, and protein activity is conducted for mutants determined computationally as being good candidates for possible BChE mutants, i.e., ones predicted to have higher catalytic efficiency as compared with wild-type BChE. In addition, mutants A199S/A328W/Y332G, A199S/F227A/A328W/Y332G, A199S/S287G/A328W/Y332G, …

Two Classes Of Nucleic Acid Translocation Motors: Rotation And Revolution Without Rotation, Peixuan Guo, Ian Grainge, Zhengyi Zhao, Mario Vieweger

Markey Cancer Center Faculty Publications

Biomotors are extensively involved in biological processes including cell mitosis, bacterial binary fission, DNA replication, DNA repair, homologous recombination, Holliday junction resolution, RNA transcription, and viral genome packaging. Traditionally, they were classified into two categories including linear and rotation motors. In 2013, a third class of motor by revolution mechanism without rotation was discovered. In this issue of "Structure and mechanisms of nanomotors in the cells", four comprehensive reviews are published to address the latest advancements of the structure and motion mechanism of a variety of biomotors in archaea, animal viruses, bacteria, and bacteriophages.

Expression Of Peroxiredoxin 1 And 4 Promotes Human Lung Cancer Malignancy, Hong Jiang, Lisha Wu, Murli Mishra, Hedy A. Chawsheen, Qiou Wei

Toxicology and Cancer Biology Faculty Publications

Members of the Peroxiredoxin (Prx) family are major cellular antioxidants that scavenge hydrogen peroxide and play essential roles in oxidative stress and cell signaling. 2-Cys Prxs, including Prx1, 2, 3 and 4, have been indicated in multiple oncogenic signaling pathways and thus may contribute to various processes of cancer development. The significance of 2-Cys Prxs in lung cancer development and their biological function in signal transduction have not been fully investigated. In this study we analyzed the expression of 2-Cys Prxs in lung cancer, and examined their levels of expression in a variety of cell lines established from human lung …

Toxoplasmosis Complications And Novel Therapeutic Synergism Combination Of Diclazuril Plus Atovaquone, Helieh S. Oz

Internal Medicine Faculty Publications

Toxoplasmosis is a major cause of foodborne disease, congenital complication, and morbidity. There is an urgent need for safe and effective therapies to encounter congenital and persisting toxoplasmosis. The hypothesis was: combination diclazuril plus atovaquone to exert a novel therapeutic synergy to prevent toxoplasmosis syndromes.

Methods: Pregnant dams were treated with diclazuril and atovaquone monotherapy or combination therapy and infected i.p with Toxoplasma tachyzoites.

RESULTS: Infected dams developed severe toxoplasmosis associated syndrome with increases in the abdominal adiposity surrounding uteri, gansterointestinal and other internal organs and excessive weight gain. Numerous organisms along with infiltration of inflammatory cells were detected …

Wound Healing: Biologics, Skin Substitutes, Biomembranes And Scaffolds, Krishna S. Vyas, Henry C. Vasconez

Surgery Faculty Publications

This review will explore the latest advancements spanning several facets of wound healing, including biologics, skin substitutes, biomembranes and scaffolds.

Calcineurin And Glial Signaling: Neuroinflammation And Beyond, Jennifer L. Furman, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

Similar to peripheral immune/inflammatory cells, neuroglial cells appear to rely on calcineurin (CN) signaling pathways to regulate cytokine production and cellular activation. Several studies suggest that harmful immune/inflammatory responses may be the most impactful consequence of aberrant CN activity in glial cells. However, newly identified roles for CN in glutamate uptake, gap junction regulation, Ca²⁺ dyshomeostasis, and amyloid production suggest that CN's influence in glia may extend well beyond neuroinflammation. The following review will discuss the various actions of CN in glial cells, with particular emphasis on astrocytes, and consider the implications for neurologic dysfunction arising with aging, injury, …

Ergovaline Stability In Tall Fescue Based On Sample Handling And Storage Methods, Krista La Moen Lea, Lori Smith, Cynthia Gaskill, Robert Coleman, S. Ray Smith

Plant and Soil Sciences Faculty Publications

Ergovaline is an ergot alkaloid produced by the endophyte Neotyphodium coenophialum (Morgan-Jones and Gams) found in tall fescue [Schedonorus arundinacea (Schreb.) Dumort.] and blamed for a multitude of livestock disorders. Ergovaline is known to be unstable and affected by many variables. The objective of this study was to determine the effect of sample handling and storage on the stability of ergovaline in tall fescue samples. Fresh tall fescue was collected from a horse farm in central Kentucky at three harvest dates and transported on ice to the University of Kentucky Veterinary Diagnostic Laboratory. Plant material was frozen in liquid …

Enhancing Immunomodulation On Innate Immunity By Shape Transition Among Rna Triangle, Square And Pentagon Nanovehicles, Emil F. Khisamutdinov, Hui Li, Daniel L. Jasinski, Jiao Chen, Jian Fu, Peixuan Guo

Center for Research on Environmental Disease Faculty Publications

Modulation of immune response is important in cancer immunotherapy, vaccine adjuvant development and inflammatory or immune disease therapy. Here we report the development of new immunomodulators via control of shape transition among RNA triangle, square and pentagon. Changing one RNA strand in polygons automatically induced the stretching of the interior angle from 60° to 90° or 108°, resulting in self-assembly of elegant RNA triangles, squares and pentagons. When immunological adjuvants were incorporated, their immunomodulation effect for cytokine TNF-α and IL-6 induction was greatly enhanced in vitro and in animals up to 100-fold, while RNA polygon controls induced unnoticeable effect. The …

Fragipan Horizon Fragmentation In Slaking Experiments With Amendment Materials And Ryegrass Root Tissue Extracts, Anastasios D. Karathanasis, Lloyd W. Murdock, Christopher J. Matocha, John H. Grove, Yvonne L. Thompson

Plant and Soil Sciences Faculty Publications

Slaking experiments were conducted of fragipan clods immersed in solutions of poultry manure, aerobically digested biosolid waste (ADB), fluidized bed combustion byproduct (FBC), D-H₂O, CaCO₃, NaF, Na-hexa-metaphosphate, and ryegrass root biomass. The fragipan clods were sampled from the Btx horizon of an Oxyaquic Fragiudalf in Kentucky. Wet sieving aggregate analysis showed significantly better fragmentation in the NaF, Na-hexa-metaphosphate, and ryegrass root solutions with a mean weight diameter range of 15.5-18.8 mm compared to the 44.2-47.9 mm of the poultry manure, ADB, and FBC treatments. Dissolved Si, Al, Fe, and Mn levels released in solution were ambiguous. …

Is Creep Feeding Lambs A Profitable Undertaking?, Donald G. Ely, Endre Fink

Agriculture and Natural Resources Publications

Creep feeding is a technique of providing feed to nursing lambs to supplement the milk they consume. Creep-fed lambs grow faster than noncreep-feds and are more aggressive in nursing ewes. This aggression stimulates greater ewe milk production which, in turn, increases creep feed intake because these lambs will be bigger at a given age.

Cytokine Gene Expression Profiles During Initiation, Progression And Resolution Of Periodontitis, Jeffrey L. Ebersole, Sreenatha S. Kirakodu, Michael John Novak, Arnold J. Stromberg, Shu Shen, Luis Orraca, Janis Gonzalez-Martinez, Armando Burgos, Octavio A. Gonzalez

Center for Oral Health Research Faculty Publications

AIM: Variations in the expression of cytokines during the progression of periodontitis remain ill-defined. We evaluated the expression of 19 cytokine genes related to T-cell phenotype/function during initiation, progression and resolution of periodontitis, and related these to the expression of soft and bone tissue destruction genes (TDGs).

MATERIALS AND METHODS: A ligature-induced periodontitis model was used in rhesus monkeys (M. mulatta) (n = 18). Gingival tissues were taken at baseline pre-ligation, 2 weeks and 1 month (Initiation) and 3 months (progression) post ligation. Ligatures were removed and samples taken 2 months later (resolution). Total RNA was isolated and the Rhesus …

Forage News [2014-09], Department Of Plant And Soil Sciences, University Of Kentucky

Forage News

• Beef Bash 2014
• Advanced KY Grazing School at Eden Shale
• 15th Kentucky Grazing Conference
• Forage Quotes and Concepts: New Book Offers Fresh Approach to Forage-Livestock Management
• U.S. Ranking in Cattle
• U.S. Alfalfa Production to Grow by 11% in 2014, USDA Reports
• Grazing Drought Stressed Corn Stalks
• Strategies to Deal with Hay Shortages

Effect Of Soil Sampling Density And Landscape Features On Soil Test Phosphorus, Donald J. Stamper, Carmen T. Agouridis, Dwayne R. Edwards, Mark A. Purschwitz

Biosystems and Agricultural Engineering Faculty Publications

Organic and/or inorganic fertilizers are used to promote crop growth yet the rate of fertilizer application is often based on the nitrogen needs of the crop and not the phosphorus needs, especially when utilizing animal manures with low N-to-P ratios as compared to plant N:P uptake. Because of this, soil phosphorus levels in many areas of the world are in excess of crop needs. Excessive levels of phosphorus in water bodies such as streams and lakes can result in a condition known as eutrophication. With eutrophication, nutrients promote algal growth which in turn decreases dissolved oxygen levels in receiving water …

Hypomagnesemic Tetany Or “Grass Tetany”, Michelle Arnold, Jeff Lehmkuhler

Agriculture and Natural Resources Publications

Magnesium is a vital component of normal nerve conduction, muscle function, and bone mineral formation. Hypomagnesemic tetany or “grass tetany” is a disorder caused by an abnormally low blood concentration of the essential mineral magnesium (Mg). Synonyms for this disorder include spring tetany, grass staggers, wheat pasture poisoning, or lactation tetany.

Lights And Larvae: Using Optogenetics To Teach Recombinant Dna And Neurobiology, John Titlow, Heidi Anderson, Robin L. Cooper

Biology Faculty Publications

Switching genes between organisms and controlling an animal’s brain using lasers may seem like science fiction, but with advancements in a technique called optogenetics, such experiments are now common in neuroscience research. Optogenetics combines recombinant DNA technology with a controlled light source to help researchers address biomedical questions in the life sciences. The technique has gained the most traction in neurobiology—the biology of the nervous system—where specific wavelengths of light are used to control or measure the activity of neurons in transgenic organisms (i.e., those with artificially inserted genes).

These optical recording and stimulation techniques are used in nervous system …

Roadway Contributing Factors In Traffic Crashes, Kenneth R. Agent

Kentucky Transportation Center Research Report

This project involved an evaluation of the codes which relate to roadway contributing factors. This included a review of relevant codes used in other states. Crashes with related codes were summarized and analyzed. A sample of crash sites was inspected to evaluate the accuracy and consistency of the data being evaluated.

The results of the study are recommendations for a coding format to enable accurate and consistent data concerning the roadway as it affected the crash as well as examples of areas of training to improve the accuracy and consistency of the data.

Recommendations relating to coding of the police …

Urbanization And Stream Salamanders: A Review, Conservation Options, And Research Needs, Kyle Barrett, Steven J. Price

Forestry and Natural Resources Faculty Publications

Urban areas are increasing in size and human population density. The implications of widespread urbanization are apparent for a wide variety of stream organisms, but the responses of stream-dwelling salamanders to urbanization have been understudied historically. Studies on this assemblage have increased sufficiently over the last decade to warrant a review and synthesis of current knowledge. Our survey of the literature indicates a research bias toward species within the Piedmont ecoregion of the USA and a strong emphasis on changes in species richness, relative abundance, and occupancy along an urbanization gradient. Very few investigators have examined vital rates for specific …

Factors Limiting The Spread Of The Protective Symbiont Hamiltonella Defensa In Aphis Craccivora Aphids, Hannah R. Dykstra, Stephanie R. Weldon, Adam J. Martinez, Jennifer A. White, Keith R. Hopper, George E. Heimpel, Mark K. Asplen, Kerry M. Oliver

Entomology Faculty Publications

Many insects are associated with heritable symbionts that mediate ecological interactions, including host protection against natural enemies. The cowpea aphid, Aphis craccivora, is a polyphagous pest that harbors Hamiltonella defensa, which defends against parasitic wasps. Despite this protective benefit, this symbiont occurs only at intermediate frequencies in field populations. To identify factors constraining H. defensa invasion in Ap. craccivora, we estimated symbiont transmission rates, performed fitness assays, and measured infection dynamics in population cages to evaluate effects of infection. Similar to results with the pea aphid, Acyrthosiphon pisum, we found no consistent costs to infection using …

Clones Of Streptococcus Zooepidemicus From Outbreaks Of Hemorrhagic Canine Pneumonia And Associated Immune Responses, Sridhar Velineni, John F. Timoney, Kim Russell, Heidi J. Hamlen, Patricia Pesavento, William D. Fortney, P. Cynda Crawford

Maxwell H. Gluck Equine Research Center Faculty Publications

Acute hemorrhagic pneumonia caused by Streptococcus zooepidemicus has emerged as a major disease of shelter dogs and greyhounds. S. zooepidemicus strains differing in multilocus sequence typing (MLST), protective protein (SzP), and M-like protein (SzM) sequences were identified from 9 outbreaks in Texas, Kansas, Florida, Nevada, New Mexico, and Pennsylvania. Clonality based on 2 or more isolates was evident for 7 of these outbreaks. The Pennsylvania and Nevada outbreaks also involved cats. Goat antisera against acutely infected lung tissue as well as convalescent-phase sera reacted with a mucinase (Sz115), hyaluronidase (HylC), InlA domain-containing cell surface-anchored protein (INLA), membrane-anchored protein (MAP), SzP, …

Fructose-2,6-Bisphosphate Synthesis By 6-Phosphofructo-2-Kinase/Fructose-2,6-Bisphosphatase 4 (Pfkfb4) Is Required For The Glycolytic Response To Hypoxia And Tumor Growth, Jason Chesney, Jennifer Clark, Alden C. Klarer, Yoannis Imbert-Fernandez, Andrew N. Lane, Sucheta Telang

Markey Cancer Center Faculty Publications

Fructose-2,6-bisphosphate (F2,6BP) is a shunt product of glycolysis that allosterically activates 6-phosphofructo-1-kinase (PFK-1) resulting in increased glucose uptake and glycolytic flux to lactate. The F2,6BP concentration is dictated by four bifunctional 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases (PFKFB1-4) with distinct kinase:phosphatase activities. PFKFB4 is over-expressed in human cancers, induced by hypoxia and required for survival and growth of several cancer cell lines. Although PFKFB4 appears to be a rational target for anti-neoplastic drug development, it is not clear whether its kinase or phosphatase activity is required for cancer cell survival. In this study, we demonstrate that recombinant human PFKFB4 kinase activity is 4.3-fold greater than …

Sex-Specific Alterations In Nos Regulation Of Vascular Function In Aorta And Mesenteric Arteries From Spontaneously Hypertensive Rats Compared To Wistar Kyoto Rats, Analia S. Loria, Krystal N. Brinson, Brandon M. Fox, Jennifer C. Sullivan

Pharmacology and Nutritional Sciences Faculty Publications

The present study tested the hypothesis that spontaneously hypertensive rats (SHR) have impaired nitric oxide synthase (NOS)-mediated regulation of vascular function versus Wistar-Kyoto rats (WKY). Aorta and small mesenteric arteries were studied from male and female SHR (M SHR and F SHR) and WKY (M WKY and F WKY). Phenylephrine (PE)-induced vasoconstriction was greater in aorta of M SHR versus all others (P < 0.05); there were neither sex nor strain differences in PE contraction in mesenteric arteries. The NOS inhibitor l-Nitro-Arginine Methyl Ester (l-NAME) increased PE-induced vasoconstriction in all rats, although the increase was the least in male SHR (P < 0.05), revealing a blunted vasoconstrictor buffering capacity of NOS. l-NAME increased sensitivity to PE-induced constriction only in mesenteric arteries of SHR, although, the maximal percent increase in contraction was comparable among groups. ACh-induced relaxation was also less in aorta from M SHR versus all others (P < 0.05). ACh relaxation was comparable among groups in mesenteric arteries, although SHR exhibited a greater NOS component to ACh-induced relaxation than WKY. To gain mechanistic insight into sex and strain differences in vascular function, NOS activity and NOS3 protein expression were measured. Aortic NOS activity was comparable between groups and M SHR had greater NOS3 expression than M WKY. In contrast, although vascular function was largely maintained in mesenteric arteries of SHR, NOS activity was less in SHR versus WKY. In conclusion, M SHR exhibit a decrease in NOS regulation of vascular function compared to F SHR and WKY, although this is not mediated by decreases in NOS activity and/or expression.

Global School-Based Childhood Obesity Interventions: A Review, Melinda J. Ickes, Jennifer Mcmullen, Taj Haider, Manoj Sharma

Kinesiology and Health Promotion Faculty Publications

Background: The issue of childhood overweight and obesity has become a global public health crisis. School-based interventions have been developed and implemented to combat this growing concern. The purpose of this review is to compare and contrast U.S. and international school-based obesity prevention interventions and highlight efficacious strategies.

Methods: A systematic literature review was conducted utilizing five relevant databases. Inclusion criteria were: (1) primary research; (2) overweight or obesity prevention interventions; (3) school-based; (4) studies published between 1 January 2002 through 31 December 2013; (5) published in the English language; (6) child-based interventions, which could include parents; and …

Applying Accelerator Mass Spectrometry For Low-Level Detection Of Complex Engineered Nanoparticles In Biological Media, Binghui Wang, George S. Jackson, Robert A. Yokel, Eric A. Grulke

Pharmaceutical Sciences Faculty Publications

Complex engineered nanoparticles (CENPs), which have different core and surface components, are being developed for medicinal, pharmaceutical and industrial applications. One of the key challenges for environmental health and safety assessments of CENPs is to identify and quantity their transformations in biological environments. This study reports the effects of in vivo exposure of citrate-coated nanoalumina with different rare isotope labels on each component. This CENP was dosed to the rat and accelerator mass spectrometry (AMS) was used to quantify ²⁶Al, ¹⁴C, and their ratio in the dosing material and tissue samples. For CENPs detected in the liver, the …

Neuroinflammation And Neurologic Deficits In Diabetes Linked To Brain Accumulation Of Amylin, Sarah Srodulski, Savita Sharma, Adam B. Bachstetter, Jennifer M. Brelsfoard, Conrado Pascual, Xinmin Simon Xie, Kathryn E. Saatman, Linda J. Van Eldik, Florin Despa

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: We recently found that brain tissue from patients with type-2 diabetes (T2D) and cognitive impairment contains deposits of amylin, an amyloidogenic hormone synthesized and co-secreted with insulin by pancreatic β-cells. Amylin deposition is promoted by chronic hypersecretion of amylin (hyperamylinemia), which is common in humans with obesity or pre-diabetic insulin resistance. Human amylin oligomerizes quickly when oversecreted, which is toxic, induces inflammation in pancreatic islets and contributes to the development of T2D. Here, we tested the hypothesis that accumulation of oligomerized amylin affects brain function.

METHODS: In contrast to amylin from humans, rodent amylin is neither amyloidogenic nor cytotoxic. …

Accountability For College And Career Readiness: Developing A New Paradigm, Linda Darling-Hammond, Gene Wilhoit, Linda Pittenger

National Center for Innovation in Education Faculty Publications

As schools across the country prepare for new standards under the Common Core, states are moving toward creating more aligned systems of assessment and accountability. This paper recommends an accountability approach that focuses on meaningful learning, enabled by professionally skilled and committed educators, and supported by adequate and appropriate resources, so that all students regardless of background are prepared for both college and career when they graduate from high school. Drawing on practices already established in other states and on the views of policymakers and school experts, this paper proposes principles for effective accountability systems and imagines what a new …

Generation And Behavior Characterization Of Camkiiβ Knockout Mice, Adam D. Bachstetter, Scott J. Webster, Tao Tu, Danielle S. Goulding, Jacques Haiech, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

The calcium/calmodulin-dependent protein kinase II (CaMKII) is abundant in the brain, where it makes important contributions to synaptic organization and homeostasis, including playing an essential role in synaptic plasticity and memory. Four genes encode isoforms of CaMKII (α, β, δ, γ), with CaMKIIα and CaMKIIβ highly expressed in the brain. Decades of molecular and cellular research, as well as the use of a large number of CaMKIIα mutant mouse lines, have provided insight into the pivotal roles of CaMKIIα in brain plasticity and cognition. However, less is known about the CaMKIIβ isoform. We report the development and extensive behavioral and …

Loss Of 4e-Bp1 Function Induces Emt And Promotes Cancer Cell Migration And Invasion Via Cap-Dependent Translational Activation Of Snail, Weijia Cai, Qing Ye, Qing-Bai She

Markey Cancer Center Faculty Publications

The cap-dependent translation is frequently deregulated in a variety of cancers associated with tumor progression. However, the molecular basis of the translation activation for metastatic progression of cancer remains largely elusive. Here, we demonstrate that activation of cap-dependent translation by silencing the translational repressor 4E-BP1 causes cancer epithelial cells to undergo epithelial-mesenchymal transition (EMT), which is associated with selective upregulation of the EMT inducer Snail followed by repression of E-cadherin expression and promotion of cell migratory and invasive capabilities as well as metastasis. Conversely, inhibition of cap-dependent translation by a dominant active mutant 4E-BP1 effectively downregulates Snail expression and suppresses …

Tombusvirus-Yeast Interactions Identify Conserved Cell-Intrinsic Viral Restriction Factors, Zsuzsanna Sasvari, Paulina Alatriste Gonzalez, Peter D. Nagy

Plant Pathology Faculty Publications

To combat viral infections, plants possess innate and adaptive immune pathways, such as RNA silencing, R gene and recessive gene-mediated resistance mechanisms. However, it is likely that additional cell-intrinsic restriction factors (CIRF) are also involved in limiting plant virus replication. This review discusses novel CIRFs with antiviral functions, many of them RNA-binding proteins or affecting the RNA binding activities of viral replication proteins. The CIRFs against tombusviruses have been identified in yeast (Saccharomyces cerevisiae), which is developed as an advanced model organism. Grouping of the identified CIRFs based on their known cellular functions and subcellular localization in yeast …

Cyclic Di-Gmp-Dependent Signaling Pathways In The Pathogenic Firmicute Listeria Monocytogenes, Li-Hong Chen, Volkan K. Köseoğlu, Zehra T. Güvener, Tanya Myers-Morales, Joseph M. Reed, Sarah E. F. D'Orazio, Kurt W. Miller, Mark Gomelsky

Microbiology, Immunology, and Molecular Genetics Faculty Publications

We characterized key components and major targets of the c-di-GMP signaling pathways in the foodborne pathogen Listeria monocytogenes, identified a new c-di-GMP-inducible exopolysaccharide responsible for motility inhibition, cell aggregation, and enhanced tolerance to disinfectants and desiccation, and provided first insights into the role of c-di-GMP signaling in listerial virulence. Genome-wide genetic and biochemical analyses of c-di-GMP signaling pathways revealed that L. monocytogenes has three GGDEF domain proteins, DgcA (Lmo1911), DgcB (Lmo1912) and DgcC (Lmo2174), that possess diguanylate cyclase activity, and three EAL domain proteins, PdeB (Lmo0131), PdeC (Lmo1914) and PdeD (Lmo0111), that possess c-di-GMP phosphodiesterase activity. Deletion of all phosphodiesterase …