Digital Commons Network^™

Methylseleninic Acid Promotes Antitumour Effects Via Nuclear Foxo3a Translocation Through Akt Inhibition, Míriam Tarrado-Castellarnau, Roldán Cortés, Miriam Zanuy, Josep Tarragó-Celada, Ibrahim H. Polat, Richard Hill, Teresa W-M Fan, Wolfgang Link, Marta Cascante

Toxicology and Cancer Biology Faculty Publications

Selenium supplement has been shown in clinical trials to reduce the risk of different cancers including lung carcinoma. Previous studies reported that the antiproliferative and pro-apoptotic activities of methylseleninic acid (MSA) in cancer cells could be mediated by inhibition of the PI3K pathway. A better understanding of the downstream cellular targets of MSA will provide information on its mechanism of action and will help to optimize its use in combination therapies with PI3K inhibitors. For this study, the effects of MSA on viability, cell cycle, metabolism, apoptosis, protein and mRNA expression, and reactive oxygen species production were analysed in A549 …

Endoplasmic Reticulum Stress And Ethanol Neurotoxicity, Fanmuyi Yang, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Ethanol abuse affects virtually all organ systems and the central nervous system (CNS) is particularly vulnerable to excessive ethanol exposure. Ethanol exposure causes profound damages to both the adult and developing brain. Prenatal ethanol exposure induces fetal alcohol spectrum disorders (FASD) which is associated with mental retardation and other behavioral deficits. A number of potential mechanisms have been proposed for ethanol-induced brain damage; these include the promotion of neuroinflammation, interference with signaling by neurotrophic factors, induction of oxidative stress, modulation of retinoid acid signaling, and thiamine deficiency. The endoplasmic reticulum (ER) regulates posttranslational protein processing and transport. The accumulation of …

Chronic Systemic Immune Dysfunction In African-Americans With Small Vessel-Type Ischemic Stroke, Candice M. Brown, Cheryl D. Bushnell, Gregory P. Samsa, Larry B. Goldstein, Carol A. Colton

Neurology Faculty Publications

The incidence of small vessel-type (lacunar) ischemic strokes is greater in African-Americans compared to whites. The chronic inflammatory changes that result from lacunar stroke are poorly understood. To elucidate these changes, we measured serum inflammatory and thrombotic biomarkers in African-Americans at least 6 weeks post-stroke compared to control individuals. Cases were African-Americans with lacunar stroke (n = 30), and controls were age-matched African-Americans with no history of stroke or other major neurologic disease (n = 37). Blood was obtained > 6 weeks post-stroke and was analyzed for inflammatory biomarkers. Freshly isolated peripheral blood mononuclear cells were stimulated with lipopolysaccharide …

Role Of B Cell Receptor Signaling In Il-10 Production By Normal And Malignant B-1 Cells., Sara S Alhakeem, Vishal J Sindhava, Mary K Mckenna, Beth W Gachuki, John C Byrd, Natarajan Muthusamy, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

B-1 cells are considered innate immune cells, which produce the majority of natural antibodies. B-1 cell responses to B cell receptor (BCR) and Toll-like receptor ligation are tightly regulated owing to the cross-reactivity to self-antigens. CD5 has been shown to play a major role in downregulation of BCR responses in B-1 cells. Here, we provide evidence for another mechanism by which BCR response is regulated in B-1 cells. B-1 cells, as well as their malignant counterpart, B cell chronic lymphocytic leukemia (B-CLL) cells, produce interleukin-10 (IL-10) constitutively. IL-10 secretion by normal B-1 cells downregulates their proliferation responses to BCR ligation. …

Prey Size And Dietary Niche Of Rafinesque's Big-Eared Bat (Corynorhinus Rafinesquii), Luke E. Dodd, Michael J. Lacki, Joseph S. Johnson, Lynne K. Rieske

Forestry and Natural Resources Faculty Publications

Bats in the genus Corynorhinus possess a suite of morphological characters that permit them to effectively use both gleaning and aerial-hawking foraging strategies to capture Lepidoptera. Consequently, they occupy a specialized feeding niche within North American bat assemblages and are of particular interest for dietary studies. We collected fecal pellets from a colony of C. rafinesquii (Rafinesque's Big-Eared Bat) at Mammoth Cave National Park during August–October 2011 and amplified cytochrome-c oxidase subunit 1 fragments of prey from these pellets. We used the Barcode of Life Database to identify prey, and evaluated the size of prey species based on published values. …

Post Operative Fungal Endopthalmitis Due To Geotrichum Candidum, Thein Myint, Matthew J. Dykhuizen, Carolyn H. Mcdonald, Julie A. Ribes

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Geotrichum species have been rarely reported as the cause of sepsis, disseminated infection in immunosuppressed patients. The patient we describe developed indolent endophthalmitis four months after her routine right eye cataract surgery. The intraoperative sample from right vitreous fluid grew Geotrichum candidum. The patient underwent vitrectomy, artificial lens explantation and intravitreal injection of amphotericin B followed by oral voriconazole. Despite these interventions, she underwent enucleation. This is the first published case of Geotrichum candidum endophthalmitis.

Effects Of Rapamycin Treatment On Neurogenesis And Synaptic Reorganization In The Dentate Gyrus After Controlled Cortical Impact Injury In Mice, Corwin R. Butler, Jeffery A. Boychuk, Bret N. Smith

Physiology Faculty Publications

Post-traumatic epilepsy (PTE) is one consequence of traumatic brain injury (TBI). A prominent cell signaling pathway activated in animal models of both TBI and epilepsy is the mammalian target of rapamycin (mTOR). Inhibition of mTOR with rapamycin has shown promise as a potential modulator of epileptogenesis in several animal models of epilepsy, but cellular mechanisms linking mTOR expression and epileptogenesis are unclear. In this study, the role of mTOR in modifying functional hippocampal circuit reorganization after focal TBI induced by controlled cortical impact (CCI) was investigated. Rapamycin (3 or 10 mg/kg), an inhibitor of mTOR signaling, was administered by intraperitoneal …

Increases In Perspective Embedding Increase Reading Time Even With Typical Text Presentation: Implications For The Reading Of Literature, D. H. Whalen, Lisa Zunshine, Michael Holquist

English Faculty Publications

Reading fiction is a major component of intellectual life, yet it has proven difficult to study experimentally. One aspect of literature that has recently come to light is perspective embedding ("she thought I left" embedding her perspective on "I left"), which seems to be a defining feature of fiction. Previous work (Whalen et al., 2012) has shown that increasing levels of embedment affects the time that it takes readers to read and understand short vignettes in a moving window paradigm. With increasing levels of embedment from 1 to 5, reading times in a moving window paradigm rose almost linearly. However, …

Epithelial Neoplasia Coincides With Exacerbated Injury And Fibrotic Response In The Lungs Of Gprc5a-Knockout Mice Following Silica Exposure, Xiaofei Wang, Dongliang Xu, Yueling Liao, Shuangshuang Zhong, Hongyong Song, Beibei Sun, Binhua P. Zhou, Jiong Deng, Baohui Han

Markey Cancer Center Faculty Publications

Exposure to crystalline silica is suggested to increase the risk for a variety of lung diseases, including fibrosis and lung cancer. However, epidemiological evidences for the exposure-risk relationship are ambiguous and conflicting, and experimental study from a reliable animal model to explore the relationship is lacking. We reasoned that a mouse model that is sensitive to both lung injury and tumorigenesis would be appropriate to evaluate the exposure-risk relationship. Previously, we showed that, Gprc5a^-/- mice are susceptible to both lung tumorigenesis and endotoxin-induced acute lung injury. In this study, we investigated the biological consequences in Gprc5a^-/- mouse model …

A Combination Approach To Treating Fungal Infections, Sanjib K. Shrestha, Marina Y. Fosso, Sylvie Garneau-Tsodikova

Pharmaceutical Sciences Faculty Publications

Azoles are antifungal drugs used to treat fungal infections such as candidiasis in humans. Their extensive use has led to the emergence of drug resistance, complicating antifungal therapy for yeast infections in critically ill patients. Combination therapy has become popular in clinical practice as a potential strategy to fight resistant fungal isolates. Recently, amphiphilic tobramycin analogues, C₁₂ and C₁₄, were shown to display antifungal activities. Herein, the antifungal synergy of C₁₂ and C₁₄ with four azoles, fluconazole (FLC), itraconazole (ITC), posaconazole (POS), and voriconazole (VOR), was examined against seven Candida albicans strains. All tested strains …

13C Tracer Studies Of Metabolism In Mouse Tumor Xenografts, Andrew N. Lane, Jun Yan, Teresa W-M Fan

Toxicology and Cancer Biology Faculty Publications

Mice are widely used for human tumor xenograft studies of cancer development and drug efficacy and toxicity. Stable isotope tracing coupled with metabolomic analysis is an emerging approach for assaying metabolic network activity. In mouse models there are several routes of tracer introduction, which have particular advantages and disadvantages that depend on the model and the questions addressed. This protocol describes the bolus i.v. route via repeated tail vein injections of solutions of stable isotope enriched tracers including ¹³C₆-glucose and ¹³C₅,¹⁵N₂-glutamine. Repeated injections give higher enrichments and over longer labeling …

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 nomicotine and N'-nitrosonornicotine (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 …

Reduced Voluntary Running Performance Is Associated With Impaired Coordination As A Result Of Muscle Satellite Cell Depletion In Adult Mice, Janna R. Jackson, Tyler J. Kirby, Christopher S. Fry, Robin L. Cooper, John J. Mccarthy, Charlotte A. Peterson, Esther E. Dupont-Versteegden

Physical Therapy Faculty Publications

BACKGROUND: Satellite cells, or muscle stem cells, have been thought to be responsible for all muscle plasticity, but recent studies using genetically modified mouse models that allow for the conditional ablation of satellite cells have challenged this dogma. Results have confirmed the absolute requirement of satellite cells for muscle regeneration but surprisingly also showed that they are not required for adult muscle growth. While the function of satellite cells in muscle growth and regeneration is becoming better defined, their role in the response to aerobic activity remains largely unexplored. The purpose of the current study was to assess the …

Early Shifts Of Brain Metabolism By Caloric Restriction Preserve White Matter Integrity And Long-Term Memory In Aging Mice, Janet Guo, Vikas Bakshi, Ai-Ling Lin

Sanders-Brown Center on Aging Faculty Publications

Preservation of brain integrity with age is highly associated with lifespan determination. Caloric restriction (CR) has been shown to increase longevity and healthspan in various species; however, its effects on preserving living brain functions in aging remain largely unexplored. In the study, we used multimodal, non-invasive neuroimaging (PET/MRI/MRS) to determine in vivo brain glucose metabolism, energy metabolites, and white matter structural integrity in young and old mice fed with either control or 40% CR diet. In addition, we determined the animals’ memory and learning ability with behavioral assessments. Blood glucose, blood ketone bodies, and body weight were also measured. We …

Mice Deficient In Endothelial Α5 Integrin Are Profoundly Resistant To Experimental Ischemic Stroke, Jill Roberts, Leon De Hoog, Gregory J. Bix

Sanders-Brown Center on Aging Faculty Publications

Stroke is a disease in dire need of better therapies. We have previously shown that a fragment of the extracellular matrix proteoglycan, perlecan, has beneficial effects following cerebral ischemia via the α5β1 integrin receptor. We now report that endothelial cell selective α5 integrin deficient mice (α5 KO) are profoundly resistant to ischemic infarct after transient middle cerebral artery occlusion. Specifically, α5 KOs had little to no infarct 2–3 days post-stroke, whereas controls had an increase in mean infarct volume over the same time period as expected. Functional outcome is also improved in the α5 KOs compared with controls. Importantly, no …

A Cytosolic Multiprotein Complex Containing P85Α Is Required For Β-Catenin Activation In Colitis And Colitis-Associated Cancer, Tatiana Goretsky, Emily M. Bradford, Hyunji Ryu, Maryam Tahir, Mary Pat Moyer, Tianyan Gao, Linheng Li, Terrence A. Barrett

Internal Medicine Faculty Publications

Wnt/β-catenin signaling is required for crypt structure maintenance. We previously observed nuclear accumulation of Ser-552 phosphorylated β-catenin (pβ-Cat^Ser-552) in intestinal epithelial cells (IEC) during colitis and colitis-associated cancer. Data here delineate a novel multiprotein cytosolic complex (MCC) involved in β-catenin signaling in the intestine. The MCC contains p85α, the class IA subunit of PI3K, along with β-catenin, 14-3-3ζ, Akt, and p110α. MCC levels in IEC increase in colitis and colitis-associated cancer patients. IEC-specific p85α-deficient (p85^ΔIEC) mice develop more severe dextran sodium …

Reliability Of Isometric And Eccentric Isokinetic Shoulder External Rotation, Brianna M. Papotto, Thomas Rice, Terry Malone, Timothy Butterfield, Tim L. Uhl

Physical Therapy Faculty Publications

CONTEXT: Shoulder external rotators are challenged eccentrically throughout the deceleration phase of throwing which is thought to contribute to overuse injuries. In order to evaluate the effectiveness of intervention programs as well as identify deficits, reliable and responsive measures of isometric and eccentric shoulder external rotation are necessary. Previously, isometric measures have primarily tested a single position and eccentric measures have not been found to have high reliability.

OBJECTIVE: To examine the between day reliability of multiple angle isometric and dynamic eccentric isokinetic testing of shoulder external rotation.

DESIGN: Repeated measures Participants: 10 healthy subjects (age: 30 ± 12 years, …

Biosafety Research For Non-Target Organism Risk Assessment Of Rnai-Based Ge Plants, Andrew F. Roberts, Yann Devos, Godwin N. Y. Lemgo, Xuguo Zhou

Entomology Faculty Publications

RNA interference, or RNAi, refers to a set of biological processes that make use of conserved cellular machinery to silence genes. Although there are several variations in the source and mechanism, they are all triggered by double stranded RNA (dsRNA) which is processed by a protein complex into small, single stranded RNA, referred to as small interfering RNAs (siRNA) with complementarity to sequences in genes targeted for silencing. The use of the RNAi mechanism to develop new traits in plants has fueled a discussion about the environmental safety of the technology for these applications, and this was the subject of …

20-Hydroxyecdysone (20e) Primary Response Gene E93 Modulates 20e Signaling To Promote Bombyx Larval-Pupal Metamorphosis, Xi Liu, Fangyin Dai, Enen Guo, Kang Li, Li Ma, Ling Tian, Yang Cao, Guozheng Zhang, Subba Reddy Palli, Sheng Li

Entomology Faculty Publications

As revealed in a previous microarray study to identify genes regulated by 20-hydroxyecdysone (20E) and juvenile hormone (JH) in the silkworm, Bombyx mori, E93 expression in the fat body was markedly low prior to the wandering stage but abundant during larval-pupal metamorphosis. Induced by 20E and suppressed by JH, E93 expression follows this developmental profile in multiple silkworm alleles. The reduction of E93 expression by RNAi disrupted 20E signaling and the 20E-induced autophagy, caspase activity, and cell dissociation in the fat body. Reducing E93 expression also decreased the expression of the 20E-induced pupal-specific cuticle protein genes and prevented growth …

Settlement-Size Scaling Among Prehistoric Hunter-Gatherer Settlement Systems In The New World, W. Randall Haas, Cynthia J. Klink, Greg J. Maggard, Mark S. Aldenderfer

Anthropology Faculty Publications

Settlement size predicts extreme variation in the rates and magnitudes of many social and ecological processes in human societies. Yet, the factors that drive human settlement-size variation remain poorly understood. Size variation among economically integrated settlements tends to be heavy tailed such that the smallest settlements are extremely common and the largest settlements extremely large and rare. The upper tail of this size distribution is often formalized mathematically as a power-law function. Explanations for this scaling structure in human settlement systems tend to emphasize complex socioeconomic processes including agriculture, manufacturing, and warfare-behaviors that tend to differentially nucleate and disperse populations …

High Activity Mutants Of Butyrylcholinesterase For Cocaine Hydrolysis, Chang-Guo Zhan, Fang Zheng, Wenchao Yang

Pharmaceutical Sciences Faculty Patents

Butyrylcholinesterase (BChE) polypeptide variants of the presently-disclosed subject matter have enhanced catalytic efficiency for (-)-cocaine, as compared to wild-type BChE. Pharmaceutical compositions of the presently-disclosed subject matter include a BChE polypeptide variant having an enhanced catalytic efficiency for (-)-cocaine. A method of the presently-disclosed subject matter for treating a cocaine-induced condition includes administering to an individual an effective amount of a BChE polypeptide variant, as disclosed herein, to lower blood cocaine concentration.

Pharmacology: The Pharmacodynamics Of Nutrients And Nutrient Interactions In Biological Functions, M. Hasan Mohajeri, Gunter P. Eckert, James R. Pauly, Christopher M. Butt

Pharmaceutical Sciences Faculty Publications

No abstract provided.

A Benign Prior Restraint Rule For Public School Classroom Speech, Scott R. Bauries

Law Faculty Scholarly Articles

This Article is a contribution to a symposium on schools and free speech. It advances the claim that the First Amendment doctrines that apply to the classroom should adopt a benign prior restraint rule. In the case of teacher classroom speech, the Garcetti rule should apply where the government’s action in interfering with the speech constitutes a prior restraint—the First Amendment should not reach such interference. In cases where a teacher first speaks and then is later punished for that speech, however, basic notions of due process and the dangers of arbitrary governmental decision making are far more pressing, and …

Forage News [2015-11], Department Of Plant And Soil Sciences, University Of Kentucky

Forage News

• Debby Dulworth as Keynote Speaker on Extending the Grazing Season at Heart of America Grazing Conference
• Study Shows No Damage to Soils from Grazing of Cover Crops
• Forage News Quote of the Month
• Get the Most out of Grazing Corn Stalks
• 2016 Kentucky Small Ruminant Grazing Conference schedule announced
• Muhlenberg County Producer and Ag Teacher to Represent Kentucky at AFGC
• Heart of America Grazing Conference Registration Open
• AGFC Annual Meeting Agenda Available

2016 Weed Control Recommendations For Kentucky Grain Crops, James R. Martin, Jonathan D. Green

Agriculture and Natural Resources Publications

The use of herbicides suggested in this publication is based on research at the Kentucky Agricultural Experiment Station and elsewhere. We have given what we believe to be the most effective herbicides, with the most suitable rates and times of application. Use of trade or brand names in this publication does not imply approval of the product to the exclusion of others which may be of similar or suitable composition.

Vegetable Production Guide For Commercial Growers, 2016-17, Shubin Saha, Emily Pfeufer, Ricardo Bessin, Shawn Wright, John Strang

Agriculture and Natural Resources Publications

Successful vegetable production generally requires the grower to make daily decisions regarding pest management, irrigation, and cultural practices. Would-be growers unwilling to make serious investments of time (and money) should not attempt to expand beyond a space at the farmers’ market. It is important for vegetable growers to have a market outlet for their product before they choose to start production. Good marketing plans start with the customer and work backward to production. Potential growers should first determine exactly what buyers want, how they want it, and when they want it. They then must determine how these crops should be …

Abcc9/Sur2 In The Brain: Implications For Hippocampal Sclerosis Of Aging And A Potential Therapeutic Target, Peter T. Nelson, Gregory A. Jicha, Wang-Xia Wang, Eseosa T. Ighodaro, Sergey C. Artiushin, Colin G. Nichols, David W. Fardo

Sanders-Brown Center on Aging Faculty Publications

The ABCC9 gene and its polypeptide product, SUR2, are increasingly implicated in human neurologic disease, including prevalent diseases of the aged brain. SUR2 proteins are a component of the ATP-sensitive potassium (“K _ATP ”) channel, a metabolic sensor for stress and/or hypoxia that has been shown to change in aging. The K _ATP channel also helps regulate the neurovascular unit. Most brain cell types express SUR2, including neurons, astrocytes, oligodendrocytes, microglia, vascular smooth muscle, pericytes, and endothelial cells. Thus it is not surprising that ABCC9 gene variants are associated with risk for human brain diseases. For example, Cantu syndrome is …

Hdl In Sepsis - Risk Factor And Therapeutic Approach, Emily E. Morin, Ling Guo, Anna Schwendeman, Xiang-An Li

Pediatrics Faculty Publications

High-density lipoprotein (HDL) is a key component of circulating blood and plays essential roles in regulation of vascular endothelial function and immunity. Clinical data demonstrate that HDL levels drop by 40-70% in septic patients, which is associated with a poor prognosis. Experimental studies using Apolipoprotein A-I (ApoAI) null mice showed that HDL deficient mice are susceptible to septic death, and overexpressing ApoAI in mice to increase HDL levels protects against septic death. These clinical and animal studies support our hypothesis that a decrease in HDL level is a risk factor for sepsis, and raising circulating HDL levels may provide an …

Connexin26 Gap Junction Mediates Mirna Intercellular Genetic Communication In The Cochlea And Is Required For Inner Ear Development, Yan Zhu, Liang Zong, Ling Mei, Hong-Bo Zhao

Otolaryngology--Head & Neck Surgery Faculty Publications

Organ development requires well-established intercellular communication to coordinate cell proliferations and differentiations. MicroRNAs (miRNAs) are small, non-coding RNAs that can broadly regulate gene expression and play a critical role in the organ development. In this study, we found that miRNAs could pass through gap junctions between native cochlear supporting cells to play a role in the cochlear development. Connexin26 (Cx26) and Cx30 are predominant isoforms and co-express in the cochlea. Cx26 deficiency but not Cx30 deficiency can cause cochlear developmental disorders. We found that associated with Cx26 deletion induced the cochlear developmental disorders, deletion of Cx26 but not Cx30 disrupted …

Interaction Of Isoflavones And Endophyte-Infected Tall Fescue Seed Extract On Vasoactivity Of Bovine Mesenteric Vasculature, Yang Jia, David L. Harmon, Michael D. Flythe, James L. Klotz

Animal and Food Sciences Faculty Publications

It was hypothesized that isoflavones may attenuate ergot alkaloid-induced vasoconstriction and possibly alleviate diminished contractility of vasculature after exposure to ergot alkaloids. The objective of this study was to determine if prior incubation of bovine mesenteric vasculature with the isoflavones formononetin (F), biochanin A (B), or an ergovaline-containing tall fescue seed extract (EXT) and their combinations affect ergotamine (ERT)-induced contractility. Multiple segments of mesenteric artery and vein supporting the ileal flange of the small intestine were collected from Angus heifers at slaughter (n = 5, bodyweight = 639 ± 39 kg). Duplicates of each vessel …