Digital Commons Network^™

Genetic Regulation Of Hematopoietic Stem Cell Aging, Erin J. Oakley

University of Kentucky Doctoral Dissertations

It is well documented that both quantitative and qualitative changes in the murine hematopoietic stem cell (HSC) population occur with age. In mice, the effect of aging on stem cells is highly strain-specific, thus suggesting genetic regulation plays a role in HSC aging. In C57BL/6 (B6) mice, the HSC population steadily increases with age, whereas in DBA/2 (D2) mice, this population declines. Our lab has previously mapped a quantitative trait locus (QTL) to murine chromosome 2 that is associated with the variation in frequency of HSCs between aged B6 and D2 mice. In these dissertation studies, I first aim to …

Roles Of Micrornas In Plant Abiotic Stress, Development And Viral Infection, Venugopal Mendu

University of Kentucky Doctoral Dissertations

Plant microRNAs play important roles in plant growth and development. Here we investigated the roles of miRNAs in the plant abiotic stress, development and viral infection. MicroRNA membrane array analysis using five different abiotic stress treatments resulted in the identification of 8 novel stress inducible miRNA-families. Functional studies on novel stress inducible miR168 revealed its functional relation with abiotic stress. Over expression of miR168 in Arabidopsis showed upregulation of four stress related miRNAs (miR163, miR167, miR398 and miR408). Analysis of 9 independent transgenic lines showed induction of miR398, an oxidative stress responsive miRNA with a corresponding down regulation of its …

Nitration And Inactivation Of Manganese Superoxide Dismutase Plays A Critical Role In Metabolic Switch, Muthuswamy Anantharaman

University of Kentucky Doctoral Dissertations

Alzheimer’s disease (AD) is a multifactorial, progressive, age-related neurodegenerative disease. Oxidative stress hypothesis is most prevalent and is gaining significant support. Inspite of the progress achieved on oxidative stress related damages in AD brain; the modification occurring on the various cellular antioxidant enzymes antioxidant has not been identified. Tyrosine nitration, a marker for peroxynitrite induced oxidative damage to protein is widespread in AD brain and Manganese superoxide dismutase (MnSOD), primary mitochondrial antioxidant enzyme is prone to peroxynitrite induced nitration and inactivation. Nitration of proteins involved in energy metabolism has been demonstrated in AD brain, which may explain the altered glucose …

The Underlying Mechanism(S) Of Fasting Induced Neuroprotection After Moderate Traumatic Brain Injury, Laurie Michelle Helene Davis

University of Kentucky Doctoral Dissertations

Traumatic brain injury (TBI) is becoming a national epidemic, as it accounts for 1.5 million cases each year. This disorder affects primarily the young population and elderly. Currently, there is no treatment for TBI, which means that ~2% of the U.S. population is currently living with prolonged neurological damage and dysfunction. Recently, there have been many studies showing that TBI negatively impacts mitochondrial function. It has been proposed that in order to save the cell from destruction mitochondrial function must be preserved. The ketogenic diet, originally designed to mimic fasting physiology, is effective in treating epilepsy. Therefore, we have used …

The Influence Of Ca2+ Regulation In Synaptic Facilitation Of Motor Nerve Terminals In Crayfish And Drosophila As Well As In The Physiological Regulation Of Larval Drosophila Heart, Mohati Desai-Shah

University of Kentucky Doctoral Dissertations

Intracellular Ca²⁺ ions are highly regulated in animal cells for them to function normally. Since the tight regulation of [Ca²⁺]i is so ubiquitous among cells, it is not surprising that altered function in [Ca²⁺]i regulation is associated with a myriad of disease states in humans. This is particularly evident in pacing myocytes and nerve terminals related to synaptic transmission. A common thread through this dissertation is on the role of three regulators proteins that are common to many cell types. These are the plasmalemmal Na⁺/Ca²⁺ exchanger (NCX), the Ca²⁺-ATPase (PMCA) …

Effect Of Chronic Airway Inflammation Induced By Allergen Sensitization On Vagal Bronchopulmonary Sensory Nerves In Rats, Guangfan Zhang

University of Kentucky Doctoral Dissertations

Airway hyperresponsivness (AHR) is one of most prominent pathophysiological features of asthma. Increasing evidence suggests that vagal bronchopulmonary afferents may be involved in the development of AHR. However, the underlying mechanisms are not clear. Therefore, the purpose of this dissertation was to investigate the effect of chronic airway inflammation induced by allergen sensitization on vagal bronchopulmonary afferents. The study was carried out in an animal model of allergic asthma. Brown-Norway rats were sensitized by intraperitoneal Ovalbumin (Ova) and exposed to aerosolized Ova 3 times/week for three weeks. Control rats received the vehicle. In vivo single-fiber recording technique was applied in …

The Role Of Stem Cell Antigen-1(Sca-1) In Muscle Aging, Sonia Angela Richards-Malcolm

University of Kentucky Master's Theses

Muscle aging is associated with a decrease in the number of satellite cells and their progeny, muscle progenitor cells (MPCs) that are available for muscle repair and regeneration. However, there is an increase in non-immuno-hematopoietic cells (CD45 negative) in regenerating muscle from aged mice characterized by high stem cell antigen -1(Sca-1) expression. In aged regenerating muscle, 14.2% of cells are CD45neg Sca-1pos while 7.2% of cells are CD45neg Sca-1pos in young adult muscle. In vitro, CD45neg Sca-1pos cells over express genes associated with fibrosis, potentially controlled by Wnt2. These cells are proliferative, non-myogenic and non-adipogenic, and arise in clonally-derived MPCs …

Use Of Parthenolide Derivatives As Antileukemic And Cytotoxic Agents, Peter A. Crooks, Craig T. Jordan, Xiaochen Wei

Pharmaceutical Sciences Faculty Patents

Compounds of the formula having anti-tumor activity, wherein R₁ and R₂ are as described herein

Methods Of Delaying Development Of Cea-Associated Tumors Using Anti-Idiotype Antibody 3h1, Malaya Chatterjee, Kenneth A. Foon, Sunil K. Chatterjee

Pharmaceutical Sciences Faculty Patents

The present invention provides methods of delaying development of CEA-associated tumors using the anti-idiotype antibody 3H1, particularly in high-risk individuals.

Pre-Mrna Secondary Structures Influence Exon Recognition, Michael Hiller, Zhaiyi Zhang, Rolf Backofen, Stefan Stamm

Molecular and Cellular Biochemistry Faculty Publications

The secondary structure of a pre-mRNA influences a number of processing steps including alternative splicing. Since most splicing regulatory proteins bind to single-stranded RNA, the sequestration of RNA into double strands could prevent their binding. Here, we analyzed the secondary structure context of experimentally determined splicing enhancer and silencer motifs in their natural pre-mRNA context. We found that these splicing motifs are significantly more single-stranded than controls. These findings were validated by transfection experiments, where the effect of enhancer or silencer motifs on exon skipping was much more pronounced in single-stranded conformation. We also found that the structural context of …

Leptospira Interrogans Endostatin-Like Outer Membrane Proteins Bind Host Fibronectin, Laminin And Regulators Of Complement, Brian Stevenson, Henry A. Choy, Marija Pinne, Matthew L. Rotondi, M. Clarke Miller, Edward Demoll, Peter Kraiczy, Anne E. Cooley, Trevor P. Creamer, Marc A. Suchard, Catherine A. Brissette, Ashutosh Verma, David A. Haake

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The pathogenic spirochete Leptospira interrogans disseminates throughout its hosts via the bloodstream, then invades and colonizes a variety of host tissues. Infectious leptospires are resistant to killing by their hosts' alternative pathway of complement-mediated killing, and interact with various host extracellular matrix (ECM) components. The LenA outer surface protein (formerly called LfhA and Lsa24) was previously shown to bind the host ECM component laminin and the complement regulators factor H and factor H-related protein-1. We now demonstrate that infectious L. interrogans contain five additional paralogs of lenA, which we designated lenB, lenC, lenD, lenE and lenF …

Allelic Heterogeneity At The Equine Kit Locus In Dominant White (W) Horses, Bianca Haase, Samantha A. Brooks, Angela Schlumbaum, Pedro J. Azor, Ernest Bailey, Ferial Alaeddine, Meike Mevissen, Dominik Burger, Pierre-André Poncet, Stefan Rieder, Tosso Leeb

Veterinary Science Faculty Publications

White coat color has been a highly valued trait in horses for at least 2,000 years. Dominant white (W) is one of several known depigmentation phenotypes in horses. It shows considerable phenotypic variation, ranging from approximately 50% depigmented areas up to a completely white coat. In the horse, the four depigmentation phenotypes roan, sabino, tobiano, and dominant white were independently mapped to a chromosomal region on ECA 3 harboring the KIT gene. KIT plays an important role in melanoblast survival during embryonic development. We determined the sequence and genomic organization of the approximately 82 kb equine KIT gene. A mutation …

Transcriptional Control Of Vascular Smooth Muscle Cell Proliferation By Peroxisome Proliferator-Activated Receptor-Γ: Therapeutic Implications For Cardiovascular Diseases, Florence Gizard, Dennis Bruemmer

Internal Medicine Faculty Publications

Proliferation of vascular smooth muscle cells (SMCs) is a critical process for the development of atherosclerosis and complications of procedures used to treat atherosclerotic diseases, including postangioplasty restenosis, vein graft failure, and transplant vasculopathy. Peroxisome proliferator-activated receptor (PPAR) gamma is a member of the nuclear hormone receptor superfamily and the molecular target for the thiazolidinediones (TZD), used clinically to treat insulin resistance in patients with type 2 diabetes. In addition to their efficacy to improve insulin sensitivity, TZD exert a broad spectrum of pleiotropic beneficial effects on vascular gene expression programs. In SMCs, PPARgamma is prominently upregulated during neointima formation …

Forage News [2007-11], Department Of Plant And Soil Sciences, University Of Kentucky

Forage News

• Kentucky Grazing Conference
• Forage Spokesman Featured at Grazing Conference
• KFGC Presents Forage Awards
• Sources for Hay
• If You Procrastinate, It May Be Too Late
• Buffalo Trace Hay Auction
• Volunteer Corn
• Winter Feeding Will Be a Challenge
• State Summary Of 2007
• Environmental Effects of Increased Atmospheric Carbon Dioxide
• Upcoming Events

The Commerciality Doctrine As Applied To The Charitable Tax Exemption For Homes For The Aged: State And Local Tax Perspectives, David A. Brennen

Law Faculty Scholarly Articles

This essay examines the question of how state and local government officials should consider federal tax law principles, like the commerciality doctrine, when they challenge state and local property tax exemptions that rely, at least in part, on tax-exempt charitable status for federal income tax purposes. In particular, this essay uses the example of continuing care retirement communities to consider tax-exempt law’s commerciality doctrine in an attempt to discern distinctions between “homes for the aged” that are “charitable,” and thus entitled to exemption, and those that are too commercial, and thus not entitled to exemption. In fact, one might say …

Techniques For Reducing Mud Problems And Improving Pasture Abused Areas, Ken Johnson

Kentucky Grazing Conference

I would like to approach this topic from two directions, mud control and then problem areas. Mud control in concentrated areas almost impossible with forages alone. Using a mud control product is usually advised. I will talk about several.

My Experiences With Summer Lovegrass, Tim Phillips

Kentucky Grazing Conference

I first heard about teff (Eragrostis tef) being used as a hay crop in early 2006 at a meeting near the Shenandoah Valley area of Virginia. The meeting was about orchardgrass production, so I was speaking about new varieties that are available for producers to grow. Several farmers had experienced massive stand losses of their established orchardgrass hay fields, so they had tried this ‘new’ summer annual grass. Some of the farmers were surprised that I knew about this grass, but I didn’t know about its use as a hay or pasture grass. Teff is the Ethiopian name for a …

Options For Summer Grazing, David C. Ditsch

Kentucky Grazing Conference

Summer is the time during the growing season when shortages of forage most often occur in Kentucky. The summer of 2007 will long be remembered as one the warmest and driest in recent years and cause many livestock producers to evaluate their current forage systems. Most Kentucky pastures are predominately cool-season grasses such as tall fescue, orchardgrass and bluegrass. During the historically hot, dry periods in July and August, these species produce very little growth and can quickly become overgrazed. At this point, some producers have no alternative except to buy feed or begin feeding stored forage intended for winter …

Does Grazing Method Matter?, Garry D. Lacefield

Kentucky Grazing Conference

Interest in and opportunities for grazing continues to increase not only in Kentucky, but throughout the U.S. In Wisconsin, 12% or approximately 5000 dairymen are now using grazing. In Michigan, over 40% of the dairymen are using grazing for a significant part of their feed requirements. Over 15% of these dairymen are using intensive grazing. Similar numbers exist for Pennsylvania.

Recovering From The "Freeze" And "Drought" Of 2007, S. Ray Smith

Kentucky Grazing Conference

As all of you know, 2007 has been a devastating year for forage agriculture in Kentucky. The season started with an abnormally warm 7 weeks during late winter and early spring, which promoted lush vegetative growth. Normally this would have been a “good thing”, but it actually made forage plants more vulnerable to below freezing temperatures. Then the severe freeze occurred, with April 7, 8, and 9 the coldest 3 day period in April in KY history. Pastures were stunted for weeks and first cut hay yields were reduced by 35 to 100%. At this point we were still hopeful …

A Non-Circadian Role For Clock-Genes In Sleep Homeostasis: A Strain Comparison, Paul Franken, Ryan Thomason, H. Craig Heller, Bruce F. O'Hara

Biology Faculty Publications

BACKGROUND: We have previously reported that the expression of circadian clock-genes increases in the cerebral cortex after sleep deprivation (SD) and that the sleep rebound following SD is attenuated in mice deficient for one or more clock-genes. We hypothesized that besides generating circadian rhythms, clock-genes also play a role in the homeostatic regulation of sleep. Here we follow the time course of the forebrain changes in the expression of the clock-genes period (per)-1, per2, and of the clock-controlled gene albumin D-binding protein (dbp) during a 6 h SD and subsequent recovery sleep in three inbred strains of mice for which …

Induction Of Insulin Secretion In Engineered Liver Cells By Nitric Oxide, Latha Muniappan, Sabire Özcan

Molecular and Cellular Biochemistry Faculty Publications

BACKGROUND: Type 1 Diabetes Mellitus results from an autoimmune destruction of the pancreatic beta cells, which produce insulin. The lack of insulin leads to chronic hyperglycemia and secondary complications, such as cardiovascular disease. The currently approved clinical treatments for diabetes mellitus often fail to achieve sustained and optimal glycemic control. Therefore, there is a great interest in the development of surrogate beta cells as a treatment for type 1 diabetes. Normally, pancreatic beta cells produce and secrete insulin only in response to increased blood glucose levels. However in many cases, insulin secretion from non-beta cells engineered to produce insulin occurs …

Forage News [2007-10], Department Of Plant And Soil Sciences, University Of Kentucky

Forage News

• Kentucky Grazing Conference
• KY Grazing Conference Hosts Popular Forage Spokesperson Contest
• Grazing Corn Stalks
• Nutrient Losses from Harvested Hay or Crop Residue
• Forages - Louisville - January - Big Event
• Biotechnology in Forage Crops: Update for KY Farmers
• The Effects of Feeding Sericea Lespedeza Hay on Growth Rate of Goats Naturally Infected with Gastrointestinal Nematodes
• Southeastern Drought Drives Search for Hay
• Upcoming Events

Agricultural Situation And Outlook Fall 2007, Chuck Corby, Kenneth H. Burdine

Agricultural Situation and Outlook

No abstract provided.

Osteopontin Mediates Obesity-Induced Adipose Tissue Macrophage Infiltration And Insulin Resistance In Mice, Takashi Nomiyama, Diego Perez-Tilve, Daisuke Ogawa, Florence Gizard, Yue Zhao, Elizabeth B. Heywood, Karrie L. Jones, Ryuzo Kawamori, Lisa A. Cassis, Matthias H. Tschöp, Dennis Bruemmer

Internal Medicine Faculty Publications

Obesity is associated with a state of chronic, low-grade inflammation characterized by abnormal cytokine production and macrophage infiltration into adipose tissue, which may contribute to the development of insulin resistance. During immune responses, tissue infiltration by macrophages is dependent on the expression of osteopontin, an extracellular matrix protein and proinflammatory cytokine that promotes monocyte chemotaxis and cell motility. In the present study, we used a murine model of diet-induced obesity to examine the role of osteopontin in the accumulation of adipose tissue macrophages and the development of insulin resistance during obesity. Mice exposed to a high-fat diet exhibited increased plasma …

A Simple Array Platform For Microrna Analysis And Its Application In Mouse Tissues, Xiaoqing Tang, Jozsef Gal, Xun Zhuang, Wang-Xia Wang, Haining Zhu, Guiliang Tang

Plant and Soil Sciences Faculty Publications

MicroRNAs (miRNAs) are a novel class of small noncoding RNAs that regulate gene expression at the post-transcriptional level and play a critical role in many important biological processes. Most miRNAs are conserved between humans and mice, which makes it possible to analyze their expressions with a set of selected array probes. Here, we report a simple array platform that can detect 553 nonredundant miRNAs encompassing the entire set of miRNAs for humans and mice. The platform features carefully selected and designed probes with optimized hybridization parameters. Potential cross-reaction between mature miRNAs and their precursors was investigated. The array platform was …

Suppression Of Peroxisomal Enzyme Activities And Cytochrome P450 4a Isozyme Expression By Congeneric Polybrominated And Polychlorinated Biphenyls, Larry W. Robertson, Isabelle Berberian, Tim Borges, Li-Chuan Chen, Ching K. Chow, Howard P. Glauert, Johannes G. Filser, Helmut Thomas

Toxicology and Cancer Biology Faculty Publications

The purpose of this study was to determine the effects of PCBs and PBBs on peroxisome proliferator-activated receptor-alpha-(PPARalpha-) associated enzyme activities or protein levels. Male Sprague-Dawley rats were administered a single IP injection (150 mu mol/kg) of either 3,3',4,4'-tetrabromobiphenyl, 3,3',4,4'-tetrachlorobiphenyl, 3,3',5,5'-tetrabromobiphenyl, 2',3,3',4,5-pentachlorobiphenyl, 3,3',4,4',5-pentachlorobiphenyl, 2,2',3,3',5,5'-hexachlorobiphenyl, or 3,3',4,4',5,5'-hexabromobiphenyl in corn oil (10 ml/kg). One week later, the activities of catalase, peroxisomal fatty acyl-CoA oxidase, and peroxisomal beta-oxidation as well as cytochrome P450 4A (CYP4A) protein content were determined in subcellular liver fractions. None of the peroxisomal enzyme activities were significantly increased by any of the halogenated biphenyl congeners tested. Except for minor …

Characterization Of The Equine 2'-5' Oligoadenylate Synthetase 1 (Oas1) And Ribonuclease L (Rnasel) Innate Immunity Genes, Jonathan J. Rios, Andrey A. Perelygin, Maureen T. Long, Teri L. Lear, Andrey A. Zharkikh, Margo A. Brinton, David L. Adelson

Veterinary Science Faculty Publications

BACKGROUND: The mammalian OAS/RNASEL pathway plays an important role in antiviral host defense. A premature stop-codon within the murine Oas1b gene results in the increased susceptibility of mice to a number of flaviviruses, including West Nile virus (WNV). Mutations in either the OAS1 or RNASEL genes may also modulate the outcome of WNV-induced disease or other viral infections in horses. Polymorphisms in the human OAS gene cluster have been previously utilized for case-control analysis of virus-induced disease in humans. No polymorphisms have yet been identified in either the equine OAS1 or RNASEL genes for use in similar case-control studies.

RESULTS: …

Forage News [2007-09], Department Of Plant And Soil Sciences, University Of Kentucky

Forage News

• Forage Spokesman Nominations
• CRP – Forage Quality
• Wet Chemistry Results of Hay Baled from CRP Fields in Hopkins Co. - Aug. 2007
• KFGC Awards
• Stockpiling Tall Fescue
• Cost Per Day on Stockpiled Fescue/Fall Fertilization
• Cost Per Day on Soyhulls/Limit Hay
• Caution When Seeding into Drought Damaged Pastures
• NAFA Summit Promotes Alfalfa for Biofuel
• Consider Annual Ryegrass as a High Quality Forage Option
• Upcoming Events

Rapid Phase Adjustment Of Melatonin And Core Body Temperature Rhythms Following A 6-H Advance Of The Light/Dark Cycle In The Horse, Barbara A. Murphy, Jeffrey A. Elliott, Dawn R. Sessions, Mandi M. Vick, Erin L. Kennedy, Barry P. Fitzgerald

Veterinary Science Faculty Publications

BACKGROUND: Rapid displacement across multiple time zones results in a conflict between the new cycle of light and dark and the previously entrained program of the internal circadian clock, a phenomenon known as jet lag. In humans, jet lag is often characterized by malaise, appetite loss, fatigue, disturbed sleep and performance deficit, the consequences of which are of particular concern to athletes hoping to perform optimally at an international destination. As a species renowned for its capacity for athletic performance, the consequences of jet lag are also relevant for the horse. However, the duration and severity of jet lag related …