Digital Commons Network^™

Ultraviolet Radiation, Aging And The Skin: Prevention Of Damage By Topical Camp Manipulation, Alexandra Amaro-Ortiz, Betty Yan, John A. D’Orazio

Markey Cancer Center Faculty Publications

Being the largest and most visible organ of the body and heavily influenced by environmental factors, skin is ideal to study the long-term effects of aging. Throughout our lifetime, we accumulate damage generated by UV radiation. UV causes inflammation, immune changes, physical changes, impaired wound healing and DNA damage that promotes cellular senescence and carcinogenesis. Melanoma is the deadliest form of skin cancer and among the malignancies of highest increasing incidence over the last several decades. Melanoma incidence is directly related to age, with highest rates in individuals over the age of 55 years, making it a clear age-related disease. …

Cytochrome P450s And Uses Thereof, Joe Chappell, Lyle F. Ralston

Plant and Soil Sciences Faculty Patents

The invention features isolated cytochrome P450 polypeptides and nucleic acid molecules, as well as expression vectors and transgenic plants containing these molecules. In addition, the invention features uses of such molecules in methods of increasing the level of resistance against a disease caused by a plant pathogen in a transgenic plant, in methods for producing altered compounds, for example, hydroxylated compounds, and in methods of producing isoprenoid compounds.

Hypoxia-Inducible Factor-1Α Restricts The Anabolic Actions Of Parathyroid Hormone, Julie L. Frey, David P. Stonko, Marie-Claude Faugere, Ryan C. Riddle

Internal Medicine Faculty Publications

The hypoxia inducible factors (Hifs) are evolutionarily conserved transcriptional factors that control homeostatic responses to low oxygen. In developing bone, Hif-1 generated signals induce angiogenesis necessary for osteoblast specification, but in mature bone, loss of Hif-1 in osteoblasts resulted in a more rapid accumulation of bone. These findings suggested that Hif-1 exerts distinct developmental functions and acts as a negative regulator of bone formation. To investigate the function of Hif-1α in osteoanabolic signaling, we assessed the effect of Hif-1α loss-of-function on bone formation in response to intermittent parathyroid hormone (PTH). Mice lacking Hif-1α in osteoblasts and osteocytes form more bone …

Activation Of C-Met And Upregulation Of Cd44 Expression Are Associated With The Metastatic Phenotype In The Colorectal Cancer Liver Metastasis Model, Victoria Allison Elliott, Piotr G. Rychahou, Yekaterina Y. Zaytseva, B. Mark Evers

Markey Cancer Center Faculty Publications

Background

Liver metastasis is the most common cause of death in patients with colorectal cancer. Despite extensive research into the biology of cancer progression, the molecular mechanisms that drive colorectal cancer metastasis are not well characterized.

Methods

HT29 LM1, HT29 LM2, HT29 LM3 cell lines were derived from the human colorectal cancer cell line HT29 following multiple rounds of in vivo selection in immunodeficient mice.

Results

CD44 expression, a transmembrane glycoprotein involved in cell-cell and cell-matrix adhesions, and cancer cells adhesion to endothelial cells was increased in all in vivo selected cell lines, with maximum CD44 expression and cancer cells …

Tanker Truck Involved In Deadly Crash On Interstate, Kentucky Injury Prevention And Research Center

Fatality Case Reports--Motor Vehicle

February 17, 2014, on a cloudy Monday, around 4:40 p.m., a 40 year-old male tanker truck driver (victim) was driving down a straight level 3-lane interstate headed north bound to a neighboring state going approximately 70 m.p.h., to deliver his 45,000 lbs. of liquid sodium sulfate when he came upon a slow moving vehicle in the right lane, the victim swerved to the left to avoid the vehicle and his 2001 Kenworth tractor trailer left the road. The victim then overcorrected and his semi flipped landing on its top in the right side of the roadway in a grassy area …

Targeting Lactate Dehydrogenase-A Inhibits Tumorigenesis And Tumor Progression In Mouse Models Of Lung Cancer And Impacts Tumor-Initiating Cells, Han Xie, Jun-Ichi Hanai, Jian-Guo Ren, Lev Kats, Kerri Burgess, Parul Bhargava, Sabina Signoretti, Julia Billiard, Kevin J. Duffy, Aaron Grant, Xiaoen Wang, Pawel Lorkiewicz, Sabrina Schatzman, Michael Bousamra, Andrew N. Lane, Richard M. Higashi, Teresa W-M Fan, Pier Paolo Pandolfi, Vikas P. Sukhatme, Pankaj Seth

Toxicology and Cancer Biology Faculty Publications

The lactate dehydrogenase-A (LDH-A) enzyme catalyzes the interconversion of pyruvate and lactate, is upregulated in human cancers, and is associated with aggressive tumor outcomes. Here we use an inducible murine model and demonstrate that inactivation of LDH-A in mouse models of NSCLC driven by oncogenic K-RAS or EGFR leads to decreased tumorigenesis and disease regression in established tumors. We also show that abrogation of LDH-A results in reprogramming of pyruvate metabolism, with decreased lactic fermentation in vitro, in vivo, and ex vivo. This was accompanied by reactivation of mitochondrial function in vitro, but not in vivo …

Sirt1 Deletion Leads To Enhanced Inflammation And Aggravates Endotoxin-Induced Acute Kidney Injury, Rong Gao, Jiao Chen, Yuxin Hu, Zhenyu Li, Shuxia Wang, Sreerama Shetty, Jian Fu

Toxicology and Cancer Biology Faculty Publications

Bacterial endotoxin has been known to induce excessive inflammatory responses and acute kidney injury. In the present study, we used a mouse model of endotoxemia to investigate the role of Sirt1 in inflammatory kidney injury. We examined molecular and cellular responses in inducible Sirt1 knockout (Sirt1-/-) mice and wild type littermates (Sirt1+/+) in lipopolysaccharide (LPS)-induced kidney injury. Our studies demonstrated that Sirt1 deletion caused aggravated kidney injury, which was associated with increased inflammatory responses including elevated pro-inflammatory cytokine production, and increased ICAM-1 and VCAM-1 expression. Inflammatory signaling such as STAT3/ERK phosphorylation and NF-κB activation was markedly elevated in kidney tissues …

Forage News [2014-05], Department Of Plant And Soil Sciences, University Of Kentucky

Forage News

• Kentucky Grazing School
• Milestone Forage Program Dates
• Hay Quality
• Mountain Ag Week at UK Robinson Center
• Forage Recovery from the Winter of 2013/14
• Hay Harvest Stage Impacts Quality
• KFGC Field Day

Lowering Somatic Cell Count With Best Management Practices, Stephen F. Higgins, Kylie Schmidt, Sarah Wightman

Agriculture and Natural Resources Publications

As health and food safety concerns grow, dairy producers are facing more stringent regulations. In 2010, the European Union (EU) set the somatic cell count (SCC) upper limit, an indicator of milk quality, for exported milk at 400,000 cells per milliliter. However, the current U.S. SCC limit is 750,000 cells per milliliter. As of January 2012, any U.S. milk used in export markets must meet the EU standards. It is projected that US milk processors will gradually adopt the EU upper limit, making it difficult for dairy producers to sell milk containing more than 400,000 somatic cells per milliliter. Dairy …

Residential Rain Gardens: Design, Construction, And Maintenance, Suzette Walling, Ashley Osborne, Brad Lee, Richard Durham

Agriculture and Natural Resources Publications

Stormwater runoff carries pollutants such as fertilizers, oil, animal waste, and dirt to local streams, lakes, and ponds and may contribute to flooding during heavy rainfall events, putting added stress on the receiving bodies of water and their ecosystems. Excess discharge impacts streams by causing erosion, destroying habitat, and deforming natural channel flow. Utilizing storage devices such as cisterns or rain barrels will minimize stormwater volume leaving your property. Contaminants discharged to streams can cause illness, impair ecological health, and increase water treatment costs.

2014-2015 Lime And Nutrient Recommendations, Lloyd W. Murdock, Edwin L. Ritchey

Agriculture and Natural Resources Publications

The recommendations found in this publication are a result of a biennial review of soil fertility research and soil test data collected in Kentucky. The committee is made up of members of the Plant and Soil Science, Horticulture, and Agricultural Economics Departments. The co-chairs of the committee and editors of this publication are Drs. Lloyd Murdock and Edwin Ritchey, Extension Soil Specialists.

Clinically Relevant Interactions Between Newer Antidepressants And Second-Generation Antipsychotics, Edoardo Spina, Jose De Leon

Psychiatry Faculty Publications

INTRODUCTION: Combinations of newer antidepressants and second-generation antipsychotics (SGAs) are frequently used by clinicians. Pharmacokinetic drug interaction (PK DI) and poorly understood pharmacodynamic (PD) drug interaction (PD DI) can occur between them.

AREAS COVERED: This paper comprehensively reviews PD DI and PK DI studies.

EXPERT OPINION: More PK DI studies are needed to better establish dose correction factors after adding fluoxetine and paroxetine to aripiprazole, iloperidone and risperidone. Further PK DI studies and case reports are also needed to better establish the need for dose correction factors after adding i) fluoxetine to clozapine, lurasidone, quetiapine and olanzapine; ii) paroxetine to …

Control Of Cellular Motility By Neuropilin-Mediated Physical Interactions, Xiaobo Li, Matthew W. Parker, Craig W. Vander Kooi

Molecular and Cellular Biochemistry Faculty Publications

The neuropilin (Nrp) family consists of multifunctional cell surface receptors with critical roles in a number of different cell and tissue types. A core aspect of Nrp function is in ligand-dependent cellular migration, where it controls the multistep process of cellular motility through integration of ligand binding and receptor signaling. At a molecular level, the role of Nrp in migration is intimately connected to the control of adhesive interactions and cytoskeletal reorganization. Here, we review the physiological role of Nrp in cellular adhesion and motility in the cardiovascular and nervous systems. We also discuss the emerging pathological role of Nrp …

Opioid-Ketamine And Norketamine Codrug Combinations For Pain Management, Joseph R. Holtman, Peter A. Crooks, Ujjwal Chakraborty

Pharmaceutical Sciences Faculty Patents

The present invention relates to the field of pain management, and more particularly to synergistic codrugs comprising an opioid and ketamine or norketamine which have been combined to form a single chemical codrug entity. When the codrug is administered it produces a synergistic analgesic response to pain.

Editors' Preface And Acknowledgments, Rachael Hoy, Christina Williams

disClosure: A Journal of Social Theory

No abstract provided.

Tapestry Of Space: Domestic Architecture And Underground Communities In Margaret Morton’S Photography Of A Forgotten New York, Irina Nersessova

disClosure: A Journal of Social Theory

This article addresses the impact urban space has on individuals through the use of Situationist International theory and psychogeography. Representations of homelessness in New York in Margaret Morton's photography are used to demonstrate the interconnectedness among space, people, and social issues. Social issues manifest themselves in urban decay, and the inhabitants react to this phenomenon emotionally and artistically. Some inhabitants demonstrate their relationship with space by responding with material production of housing and art, which they accomplish by building without exploiting the environment the way the manufacturing of commodities often does.

Noncanonical Role For The Host Vps4 Aaa+ Atpase Escrt Protein In The Formation Of Tomato Bushy Stunt Virus Replicase, Daniel Barajas, Isabel Fernández De Castro Martín, Judit Pogany, Cristina Risco, Peter D. Nagy

Plant Pathology Faculty Publications

Assembling of the membrane-bound viral replicase complexes (VRCs) consisting of viral- and host-encoded proteins is a key step during the replication of positive-stranded RNA viruses in the infected cells. Previous genome-wide screens with Tomato bushy stunt tombusvirus (TBSV) in a yeast model host have revealed the involvement of eleven cellular ESCRT (endosomal sorting complexes required for transport) proteins in viral replication. The ESCRT proteins are involved in endosomal sorting of cellular membrane proteins by forming multiprotein complexes, deforming membranes away from the cytosol and, ultimately, pinching off vesicles into the lumen of the endosomes. In this paper, we show an …

Acetobixan, An Inhibitor Of Cellulose Synthesis Identified By Microbial Bioprospecting, Ye Xia, Lei Lei, Chad Brabham, Jozsef Stork, James R. Strickland, Adam Ladak, Ying Gu, Ian Wallace, Seth Debolt

Horticulture Faculty Publications

In plants, cellulose biosynthesis is an essential process for anisotropic growth and therefore is an ideal target for inhibition. Based on the documented utility of small-molecule inhibitors to dissect complex cellular processes we identified a cellulose biosynthesis inhibitor (CBI), named acetobixan, by bio-prospecting among compounds secreted by endophytic microorganisms. Acetobixan was identified using a drug-gene interaction screen to sift through hundreds of endophytic microbial secretions for one that caused synergistic reduction in root expansion of the leaky AtcesA6prc1-1 mutant. We then mined this microbial secretion for compounds that were differentially abundant compared with Bacilli that failed to mimic CBI action …

Everything Is Permitted? People Intuitively Judge Immorality As Representative Of Atheists, Will M. Gervais

Psychology Faculty Publications

Scientific research yields inconsistent and contradictory evidence relating religion to moral judgments and outcomes, yet most people on earth nonetheless view belief in God (or gods) as central to morality, and many view atheists with suspicion and scorn. To evaluate intuitions regarding a causal link between religion and morality, this paper tested intuitive moral judgments of atheists and other groups. Across five experiments (N = 1,152), American participants intuitively judged a wide variety of immoral acts (e.g., serial murder, consensual incest, necrobestiality, cannibalism) as representative of atheists, but not of eleven other religious, ethnic, and cultural groups. Even atheist …

Multi-Tgdr, A Multi-Class Regularization Method, Identifies The Metabolic Profiles Of Hepatocellular Carcinoma And Cirrhosis Infected With Hepatitis B Or Hepatitis C Virus, Suyan Tian, Howard H. Chang, Chi Wang, Jing Jiang, Xiaomei Wang, Junqi Niu

Biostatistics Faculty Publications

BACKGROUND: Over the last decade, metabolomics has evolved into a mainstream enterprise utilized by many laboratories globally. Like other "omics" data, metabolomics data has the characteristics of a smaller sample size compared to the number of features evaluated. Thus the selection of an optimal subset of features with a supervised classifier is imperative. We extended an existing feature selection algorithm, threshold gradient descent regularization (TGDR), to handle multi-class classification of "omics" data, and proposed two such extensions referred to as multi-TGDR. Both multi-TGDR frameworks were used to analyze a metabolomics dataset that compares the metabolic profiles of hepatocellular carcinoma (HCC) …

Expression, Purification And Characterization Of Soluble Red Rooster Laforin As A Fusion Protein In Escherichia Coli, M. Kathryn Brewer, Satrio Husodo, Vikas V. Dukhande, Mary Beth Johnson, Matthew S. Gentry

Molecular and Cellular Biochemistry Faculty Publications

BACKGROUND: The gene that encodes laforin, a dual-specificity phosphatase with a carbohydrate-binding module, is mutated in Lafora disease (LD). LD is an autosomal recessive, fatal progressive myoclonus epilepsy characterized by the intracellular buildup of insoluble, hyperphosphorylated glycogen-like particles, called Lafora bodies. Laforin dephosphorylates glycogen and other glucans in vitro, but the structural basis of its activity remains unknown. Recombinant human laforin when expressed in and purified from E. coli is largely insoluble and prone to aggregation and precipitation. Identification of a laforin ortholog that is more soluble and stable in vitro would circumvent this issue.

RESULTS: In this study, we …

Comparative Analysis Of Gingival Tissue Antigen Presentation Pathways In Ageing And Periodontitis, Octavio A. Gonzalez, Michael John Novak, Sreenatha S. Kirakodu, Luis Orraca, Kuey-Chu Chen, Arnold J. Stromberg, Janis Gonzalez-Martinez, Jeffrey L. Ebersole

Center for Oral Health Research Faculty Publications

AIM: Gingival tissues of periodontitis lesions contribute to local elevations in mediators, including both specific T cell and antibody immune responses to oral bacterial antigens. Thus, antigen processing and presentation activities must exist in these tissues to link antigen-presenting cells with adaptive immunity. We hypothesized that alterations in the transcriptome of antigen processing and presentation genes occur in ageing gingival tissues and that periodontitis enhances these differences reflecting tissues less capable of immune resistance to oral pathogens.

MATERIALS AND METHODS: Rhesus monkeys (n = 34) from 3 to 23 years of age were examined. A buccal gingival sample from healthy …

Global Kentucky (Spring 2014), University Of Kentucky International Center

Global Kentucky

No abstract provided.

Increasing Dry Cow And Bred Heifer Performance With Environmental Management, Stephen F. Higgins, Kylie Schmidt

Agriculture and Natural Resources Publications

Producing high-quality milk is a primary concern of dairy farmers, which is why the production herd often receives more attention than the dry cows and bred heifers. However, it is important that dairy producers not lose sight of the great value that their dry cows and bred heifers hold: the future of the milking herd. Environmental management practices such as rotational grazing, heavy-use area pads for feeding and watering, and shelter can be used to increase close-up cows’ future performance by preventing mastitis and other health disorders such as lameness.

Cyanide Poisoning In Ruminants, Michelle Arnold, Cynthia Gaskill, S. Ray Smith, Garry D. Lacefield

Agriculture and Natural Resources Publications

Prussic acid, cyanide, or hydrocyanic acid are all terms relating to the same toxic substance. Hydrogen cyanide was first isolated from a blue dye (Prussian blue) and because of its acidic nature it became known by the common name “prussic acid.” Cyanide is one of the most rapidly acting toxins that affect cattle.

Collection And Preparation Of Milk Samples For Microbiological Culturing [2014], Jeffrey M. Bewley, Robert J. Harmon, Stephan Locke, Michelle Arnold

Agriculture and Natural Resources Publications

In developing individual farm mastitis control and treatment strategies, it is often necessary to characterize the types of bacteria that are present on your farm. To answer this question, a microbiological analysis, or milk culture, must be performed on milk samples collected from cows showing clinical signs of mastitis or with elevated somatic cell counts. Results of the milk cultures will help identify which bacteria are causing the mastitis. In turn, this information can be used to alter mastitis control, prevention, and treatment options to fit your herd’s conditions.

Ergotism, Michelle Arnold

Agriculture and Natural Resources Publications

Ergotism and fescue toxicosis are clinically similar syndromes caused by consuming plants containing ergot alkaloids. The toxic effects and mechanisms of action are similar in both syndromes although the alkaloids are produced by different species of fungi. Ergot is a fungus that grows on the seed head of cereal grains and grasses. The term “ergot” is used in general as a common name for the Claviceps fungi or it may be used more specifically when referring to the ergot body of Claviceps purpurea when present on rye. These fungi parasitize the ovary of the developing grass flower and prevent development …

Southeastern Law Librarian Spring 2014, Seaall

Newsletters

No abstract provided.

Firesetting Behavior And Associated Comorbid Psychiatric Disorders, Stephanie Stockburger, Hatim A. Omar

Pediatrics Faculty Publications

Firesetting behavior results in serious damage to lives and property every year. Firesetting has been linked to a number of comorbid psychiatric disorders including depression, substance abuse, conduct disorder, antisocial personality disorder, obsessive compulsive disorder, psychotic disorder, schizoid personality disorder, and schizophrenia. Psychiatric disorders differ by gender. In addition, juvenile firesetters have history of a separate set of psychiatric comorbidities. The strong correlation between psychiatric comorbidities and firesetting behavior illustrates the need for fire service and mental health collaboration.

Bisphenol A Increases Atherosclerosis In Pregnane X Receptor-Humanized Apoe Deficient Mice, Yipeng Sui, Se-Hyung Park, Robert N. Helsley, Manjula Sunkara, Frank J. Gonzalez, Andrew J. Morris, Changcheng Zhou

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Bisphenol A (BPA) is a base chemical used extensively in many consumer products. BPA has recently been associated with increased risk of cardiovascular disease (CVD) in multiple large-scale human population studies, but the underlying mechanisms remain elusive. We previously reported that BPA activates the pregnane X receptor (PXR), which acts as a xenobiotic sensor to regulate xenobiotic metabolism and has pro-atherogenic effects in animal models upon activation. Interestingly, BPA is a potent agonist of human PXR but does not activate mouse or rat PXR signaling, which confounds the use of rodent models to evaluate mechanisms of BPA-mediated CVD risk. …