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Sumo Regulates The Activity Of Smoothened And Costal-2 In Drosophila Hedgehog Signaling, Jie Zhang, Yajuan Liu, Kai Jiang, Jianhang Jia

Markey Cancer Center Faculty Publications

In Hedgehog (Hh) signaling, the GPCR-family protein Smoothened (Smo) acts as a signal transducer that is regulated by phosphorylation and ubiquitination, which ultimately change the cell surface accumulation of Smo. However, it is not clear whether Smo is regulated by other post-translational modifications, such as sumoylation. Here, we demonstrate that knockdown of the small ubiquitin-related modifier (SUMO) pathway components Ubc9 (a SUMO-conjugating enzyme E2), PIAS (a SUMO-protein ligase E3), and Smt3 (the SUMO isoform in Drosophila) by RNAi prevents Smo accumulation and alters Smo activity in the wing. We further show that Hh-induced-sumoylation stabilizes Smo, whereas desumoylation by Ulp1 …

A Novel Educational Module To Teach Neural Circuits For College And High School Students: Ngss-Neurons, Genetics, And Selective Stimulations, Zana R. Majeed, Felicitas Koch, Joshua Morgan, Heidi Anderson, Jennifer Wilson, Robin L. Cooper

Biology Faculty Publications

This report introduces various approaches to target defined neural pathways for stimulation and to address the effect of particular neural circuits on behavior in a model animal, the fruit fly (Drosophila melanogaster). The objective of this novel educational module described can be used to explain and address principle concepts in neurobiology for high school and college level students. A goal of neurobiology is to show how neural circuit activity controls corresponding behavior in animals. The fruit fly model system provides powerful genetic tools, such as the UAS-Gal4 system, to manipulate expression of non-native proteins in various populations of …

A Quantitative Lc-Ms/Ms Method For Simultaneous Determination Of Cocaine And Its Metabolites In Whole Blood, Xiabin Chen, Xirong Zheng, Kai Ding, Ziyuan Zhou, Chang-Guo Zhan, Fang Zheng

Molecular Modeling and Biopharmaceutical Center Faculty Publications

As new metabolic pathways of cocaine were recently identified, a high performance liquid chromatography tandem mass spectrometry (LC–MS/MS) method was developed to simultaneously determine cocaine and nine cocaine-related metabolites in whole blood samples. One-step solid phase extraction was used to extract all of the ten compounds and corresponding internal standards from blood samples. All compounds and internal standards extracted were separated on an Atlantis T3 (100 Å, 3 μm, 2.1 mm × 150 mm I.D) column and detected in positive ion and high sensitivity mode with multiple reaction monitoring. This method was validated for its sensitivity, linearity, specificity, accuracy, precision, …

Adipocytes Activate Mitochondrial Fatty Acid Oxidation And Autophagy To Promote Tumor Growth In Colon Cancer, Yang-An Wen, Xiaopeng Xing, Jennifer W. Harris, Yekaterina Y. Zaytseva, Mihail I. Mitov, Dana L. Napier, Heidi L. Weiss, B. Mark Evers, Tianyan Gao

Markey Cancer Center Faculty Publications

Obesity has been associated with increased incidence and mortality of a wide variety of human cancers including colorectal cancer. However, the molecular mechanism by which adipocytes regulate the metabolism of colon cancer cells remains elusive. In this study, we showed that adipocytes isolated from adipose tissues of colon cancer patients have an important role in modulating cellular metabolism to support tumor growth and survival. Abundant adipocytes were found in close association with invasive tumor cells in colon cancer patients. Co-culture of adipocytes with colon cancer cells led to a transfer of free fatty acids that released from the adipocytes to …

Forage News [2017-02], Department Of Plant And Soil Sciences, University Of Kentucky

Forage News

• Dr. Chris Teutsch - New Forage Extension Specialist
• Benefits of Clovers: Cattle Health and Increased Production
• Industrial Hemp - Any Potential as Forage?

Ergot And Loline Alkaloid Concentrations In Endophyte-Infected Tall Fescue Tillers, Rebecca L. Mcculley

Forage Climate Change Experiment Research Data

Approximately 40 tall fescue tillers were randomly collected and frozen from each of the 20 treatment plots.

Tillers were cut at 7.6 cm above ground level and tested for the presence of the Epichloe endophyte using an enzyme-linked immunosorbent assay.

Tillers from each plot were sorted into 'infected' vs 'uninfected' groups, lyophilized, and ground through a 1mm screen using a Cyclotec 1093 mill.

Ground material from the endophyte infected tillers was analyzed for ergot and loline alkaloids in the lab of Lowell Bush at the University of Kentucky, Plant and Soil Sciences Dept.

For details on alkaloid analyses see: McCulley …

Seed Biology And Yield Of Grain Crops, Dennis B. Egli

Plant and Soil Sciences Faculty Book Gallery

Description from CABI (Centre for Agriculture and Biosciences International):

This new edition of an established title examines the determination of grain crop yield from a unique perspective, by concentrating on the influence of the seed itself. As the food supply for an expanding world population is based on grain crops harvested for their seeds, understanding the process of seed growth and its regulation is crucial to our efforts to increase production and meet the needs of that population. Yield of grain crops is determined by their assimilatory processes such as photosynthesis and the biosynthetic processes in the seed, which are …

Correcting The Trajectory Of Stroke Therapeutic Research, Keith R. Pennypacker, Gregory J. Bix, Justin F. Fraser

Neurology Faculty Publications

No abstract provided.

The Effect Of Sazetidine-A And Other Nicotinic Ligands On Nicotine Controlled Goal-Tracking In Female And Male Rats, S. Charntikov, A. M. Falco, K. Fink, Linda P. Dwoskin, R. A. Bevins

Pharmaceutical Sciences Faculty Publications

Nicotine is the primary addictive component of tobacco products and its complex stimulus effects are readily discriminated by humans and non-human animals. Previous preclinical research investigating directly the nature of the nicotine stimulus has been limited to male rodents. The current study began to address this significant gap in the literature by training female and male rats to discriminate 0.4 mg/kg nicotine from saline in the discriminated goal-tracking task. In this task, access to sucrose was intermittently available on nicotine session. On saline session, intermixed with nicotine sessions on separate days, sucrose was not available. Both sexes acquired the discrimination …

Nephrotoxicity During Vancomycin Therapy In Combination With Piperacillin-Tazobactam Or Cefepime, Wilbur Cliff Rutter, Jessica N. Cox, Craig A. Martin, Donna R. Burgess, David S. Burgess

Pharmacy Practice and Science Faculty Publications

Recent reports have demonstrated that vancomycin (VAN) may lead to an increase in the incidence of acute kidney injury (AKI) when it is combined with antipseudomonal beta-lactams. This study compared the incidence of AKI associated with VAN plus piperacillin-tazobactam (TZP) or cefepime (FEP). This was a retrospective, matched cohort study that was conducted at an academic medical center between September 2010 and September 2014 and that included adult patients without severe chronic or structural kidney disease, dialysis, pregnancy, cystic fibrosis, or a hospital transfer receiving TZP-VAN or FEP-VAN for at least 48 h. The primary outcome was the difference in …

Early Gadolinium Enhancement For Area At Risk Determination: A Preclinical Validation Study, Sophia Hammer-Hansen, Steve W. Leung, Li-Yueh Hsu, Joel R. Wilson, Joni Taylor, Anders M. Greve, Jens Jakob Thune, Lars Køber, Peter Kellman, Andrew E. Arai

Internal Medicine Faculty Publications

Objectives—The aim of this study was to determine if early gadolinium enhancement (EGE) by cardiovascular magnetic resonance (CMR) imaging in a canine model of reperfused myocardial infarction depicts the area at risk (AAR) as determined by microsphere blood flow analysis.

Background—It remains controversial whether only the irreversibly injured myocardium enhances when performing CMR imaging in the setting of acute myocardial infarction. Recently, EGE has been proposed as a measure of the AAR in acute myocardial infarction as it correlates well with T2-weighted imaging of the AAR, but still requires pathological validation.

Methods—Eleven dogs underwent 2 hours of …

Myocardial Relaxation Is Accelerated By Fast Stretch, Not Reduced Afterload, Charles S. Chung, Charles W. Hoopes, Kenneth S. Campbell

Physiology Faculty Publications

Fast relaxation of cross-bridge generated force in the myocardium facilitates efficient diastolic function. Recently published research studying mechanisms that modulate the relaxation rate has focused on molecular factors. Mechanical factors have received less attention since the 1980s when seminal work established the theory that reducing afterload accelerates the relaxation rate. Clinical trials using afterload reducing drugs, partially based on this theory, have thus far failed to improve outcomes for patients with diastolic dysfunction. Therefore, we reevaluated the protocols that suggest reducing afterload accelerates the relaxation rate and identified that myocardial relengthening was a potential confounding factor. We hypothesized that the …

Inducible Nitric Oxide Synthase (Inos) Is A Novel Negative Regulator Of Hematopoietic Stem/Progenitor Cell Trafficking, Mateusz Adamiak, Ahmed Abdelbaset-Ismail, Joseph B. Moore Iv, J. Zhao, Ahmed Abdel-Latif, Marcin Wysoczynski, Mariusz Z. Ratajczak

Internal Medicine Faculty Publications

Nitric oxide (NO) is a gaseous free radical molecule involved in several biological processes related to inflammation, tissue damage, and infections. Based on reports that NO inhibits migration of granulocytes and monocytes, we became interested in the role of inducible NO synthetase (iNOS) in pharmacological mobilization of hematopoietic stem/progenitor cells (HSPCs) from bone marrow (BM) into peripheral blood (PB). To address the role of NO in HSPC trafficking, we upregulated or downregulated iNOS expression in hematopoietic cell lines. Next, we performed mobilization studies in iNOS^−/− mice and evaluated engraftment of iNOS^−/− HSPCs in wild type (control) animals. Our …

Obesity: Current And Potential Pharmacotherapeutics And Targets, Vidya Narayanaswami, Linda P. Dwoskin

Pharmaceutical Sciences Faculty Publications

Obesity is a global epidemic that contributes to a number of health complications including cardiovascular disease, type 2 diabetes, cancer and neuropsychiatric disorders. Pharmacotherapeutic strategies to treat obesity are urgently needed. Research over the past two decades has increased substantially our knowledge of central and peripheral mechanisms underlying homeostatic energy balance. Homeostatic mechanisms involve multiple components including neuronal circuits, some originating in hypothalamus and brain stem, as well as peripherally-derived satiety, hunger and adiposity signals that modulate neural activity and regulate eating behavior. Dysregulation of one or more of these homeostatic components results in obesity. Coincident with obesity, reward mechanisms …

Pneumocystis Infection Alters The Activation State Of Pulmonary Macrophages, Jessica M. Deckman, Cathryn J. Kurkjian, Joseph P. Mcgillis, Theodore J. Cory, Susan E. Birket, Linda M. Schutzman, Brian S. Murphy, Beth A. Garvy, David J. Feola

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Recent studies show a substantial incidence of Pneumocystis jirovecii colonization and infection in patients with chronic inflammatory lung conditions. However, little is known about the impact of Pneumocystis upon the regulation of pulmonary immunity. We demonstrate here that Pneumocystis polarizes macrophages towards an alternatively activated macrophage-like phenotype. Genetically engineered mice that lack the ability to signal through IL-4 and IL-13 were used to show that Pneumocystis alternative macrophage activation is dependent upon signaling through these cytokines. To determine whether Pneumocystis-induced macrophage polarization would impact subsequent immune responses, we infected mice with Pneumocystis and then challenged them with Pseudomonas aeruginosa 14 …

Safety And Improvement Of Movement Function After Stroke With Atomoxetine: A Pilot Randomized Trial, Andrea Ward, Cheryl Carrico, Elizabeth Powell, Philip M. Westgate, Laurie Nichols, Anne Fleischer, Lumy Sawaki

Physical Medicine and Rehabilitation Faculty Publications

Background: Intensive, task-oriented motor training has been associated with neuroplastic reorganization and improved upper extremity movement function after stroke. However, to optimize such training for people with moderate-to-severe movement impairment, pharmacological modulation of neuroplasticity may be needed as an adjuvant intervention.

Objective: Evaluate safety, as well as improvement in movement function, associated with motor training paired with a drug to upregulate neuroplasticity after stroke.

Methods: In this double-blind, randomized, placebo-controlled study, 12 subjects with chronic stroke received either atomoxetine or placebo paired with motor training. Safety was assessed using vital signs. Upper extremity movement function was assessed using Fugl-Meyer Assessment, …

Effects Of Litter On Seedling Emergence And Seed Persistence Of Three Common Species On The Loess Plateau In Northwestern China, Rui Zhang, Xiaowen Hu, Jerry M. Baskin, Carol C. Baskin, Yanrong Wang

Biology Faculty Publications

Litter accumulation resulting from land use change (enclosure) is one of the key variables influencing seedling recruitment and consequently the regeneration of plant populations and seed persistence in the soil seed bank. A better understanding of the effects of litter on seed germination and seedling emergence is crucial for developing a new set of indicators for grassland ecosystem health and for grassland management policy. We investigated the effects of seed position in litter and amount of litter covering the seed on seedling emergence and seed persistence of three common species on the Loess Plateau in northwestern China. Seed position beneath …

Sodium-Myoinositol Cotransporter-1, Smit1, Mediates The Production Of Reactive Oxygen Species Induced By Hyperglycemia In The Heart, Anne Van Steenbergen, Magali Balteau, Audrey Ginion, Laura Ferté, Sylvain Battault, Christophe De Meester De Ravenstein, Jean-Luc Balligand, Evangelos-Panagiotis Daskalopoulos, Patrick Gilon, Florin Despa, Sanda Despa, Jean-Louis Vanoverschelde, Sandrine Horman, Hermann Koepsell, Gerard Berry, Louis Hue, Luc Bertrand, Christophe Beauloye

Pharmacology and Nutritional Sciences Faculty Publications

Hyperglycemia (HG) stimulates the production of reactive oxygen species in the heart through activation of NADPH oxidase 2 (NOX2). This production is independent of glucose metabolism but requires sodium/glucose cotransporters (SGLT). Seven SGLT isoforms (SGLT1 to 6 and sodium-myoinositol cotransporter-1, SMIT1) are known, although their expression and function in the heart remain elusive. We investigated these 7 isoforms and found that only SGLT1 and SMIT1 were expressed in mouse, rat and human hearts. In cardiomyocytes, galactose (transported through SGLT1) did not activate NOX2. Accordingly, SGLT1 deficiency did not prevent HG-induced NOX2 activation, ruling it out in the cellular response to …

Data Management Basics And Best Practices, Christie Peters

Research Data and Scholarly Communications Committee Workshops

Big data, data management, and data life cycle are all buzzwords being discussed among librarians, researchers, and campus administrators across the country and around the world. Learn the basics of these terms and what services an academic library system might be expected to offer patrons, while identifying personal opportunities for improving how you work with your own data. You will have the opportunity to explore DMPTool during this session.

The presentation slides are available by clicking the Download button on the right. Handouts as well as the video and audio files of this workshop are listed as additional files below …

Neurovascular Astrocyte Degeneration In The Hyperhomocysteinemia Model Of Vascular Cognitive Impairment And Dementia (Vcid), Tiffany L. Sudduth, Erica M. Weekman, Brittani Rae Price, Jennifer L. Gooch, Abigail E. Woolums, Christopher M. Norris, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

Vascular cognitive impairment and dementia (VCID) is the second leading cause of dementia behind Alzheimer’s disease (AD) and is a frequent co-morbidity with AD. Despite its prevalence, little is known about the molecular mechanisms underlying the cognitive dysfunction resulting from cerebrovascular disease. Astrocytic end-feet almost completely surround intraparenchymal blood vessels in the brain and express a variety of channels and markers indicative of their specialized functions in the maintenance of ionic and osmotic homeostasis and gliovascular signaling. These functions are mediated by end-foot enrichment of the aquaporin 4 water channel (AQP4), the inward rectifying potassium channel Kir4.1 and the calcium-dependent …

Seed Dormancy-Breaking In A Cold Desert Shrub In Relation To Sand Temperature And Moisture, Huiliang Liu, Buhailiqiemu Abudureheman, Lingwei Zhang, Jerry M. Baskin, Carol C. Baskin, Daoyuan Zhang

Biology Faculty Publications

Seasonal periodicity of seed germination and its relationship to seasonal changes in temperature and soil moisture have been well studied in seeds of species with physiological dormancy. However, relatively little information is available on the role of these environmental factors in controlling germination of seeds with physical dormancy (PY). Our primary aim was to determine if seeds of the cold desert sand dune semi-shrub Eremosparton songoricum exhibits seasonal periodicity of seed germination and the relationship between seed dormancy break and soil temperature and moisture. In the laboratory, seeds incubated on dry, wet, wet-dry and dry-wet sand were exposed to a …

Translational Models For Vascular Cognitive Impairment: A Review Including Larger Species, Atticus H. Hainsworth, Stuart M. Allan, Johannes Boltze, Catriona Cunningham, Chad Farris, Elizabeth Head, Masafumi Ihara, Jeremy D. Isaacs, Raj N. Kalaria, Saskia A. M. J. Lesnik Oberstein, Mark B. Moss, Björn Nitzsche, Gary A. Rosenberg, Julie W. Rutten, Melita Salkovic-Petrisic, Aron M. Troen

Pharmacology and Nutritional Sciences Faculty Publications

Background: Disease models are useful for prospective studies of pathology, identification of molecular and cellular mechanisms, pre-clinical testing of interventions, and validation of clinical biomarkers. Here, we review animal models relevant to vascular cognitive impairment (VCI). A synopsis of each model was initially presented by expert practitioners. Synopses were refined by the authors, and subsequently by the scientific committee of a recent conference (International Conference on Vascular Dementia 2015). Only peer-reviewed sources were cited.

Methods: We included models that mimic VCI-related brain lesions (white matter hypoperfusion injury, focal ischaemia, cerebral amyloid angiopathy) or reproduce VCI risk factors (old age, hypertension, …

Mono Quaternary Ammonium Salts And Methods For Modulating Neuronal Nicotinic Acetylcholine Receptors, Peter A. Crooks, Linda P. Dwoskin, Guangrong Zheng, Sangeetha Sumithran, Zhenfa Zheng

Pharmaceutical Sciences Faculty Patents

Provided are monoquaternary ammonium compounds which are modulators of nicotinic acetylcholine receptors. Also provided are methods of using the compounds for modulating the function of a nicotinic acetylcholine receptor, and for the prevention and/or treatment of central nervous system disorders, substance use and/or abuse, and gastrointestinal tract disorders.

How To Maximize Energy Content In Forage Grasses, S. Ray Smith, Kelly Prince

Forage Symposium at the Kentucky Cattlemen’s Convention

In a recent paper, Kathryn Watts and Jerry Chatterton (2004) gave an excellent overview of the basic factors affecting carbohydrate levels in forages and how these factors affect forage management.

• Sugars are the substrates for all plant growth, thus, they are critical to plant growth and development.
• Sugars are produced by photosynthesis during daylight.
• At night plants use energy from sugars formed by photosynthesis to grow.
• Whenever the rates of photosynthesis exceed plant growth rates, carbohydrates accumulate.
• At times, plant stresses decrease growth rates more than photosynthesis and carbohydrates accumulate.
• Factors that contribute to plant stress include water and nutrient …

Building A Year Round Grazing System, Christopher D. Teutsch

Forage Symposium at the Kentucky Cattlemen’s Convention

There are three basic ways to increase net returns in ruminant livestock operations. The first is to increase the price we get for our product. Unfortunately in a commodity based system we have little or no control over the price that we receive. The second is to increase total production. By producing more units that have a slim profit margin we can increase net returns. However, at some point we become resource limited; we run out of land or time. The third is to control production costs. Of these three ways to increase net returns, this one has the greatest …

Promote Growth And Animal Health With Isoflavones In Red Clover And Other Legumes, Michael D. Flythe, Glen E. Aiken

Forage Symposium at the Kentucky Cattlemen’s Convention

The field of nutrition has continued to expand since the 18th century. We once thought that the only important components in foods and feeds were proteins, carbohydrates, fats and salts. Evidence was slowly pieced together to show that certain minor components were essential for life, and the vitamins were discovered. Like the doctors that first suspected vitamins were essential, some cattlemen have long noted advantages in animal performance and health on certain diets in ways that cannot be explained by a simple forage analysis. Today, we are learning the roles that phenolic plant secondary metabolites, sometimes called polyphenols, play in …

Foreword [2017], S. Ray Smith, Krista Lea

Forage Symposium at the Kentucky Cattlemen’s Convention

This is the front matter of the proceedings.

Moderator Biographies, Heart Of America Grazing Conference

Kentucky Grazing Conference

No abstract provided.

Grazing Panel, Jeff Beasley, Trevor Toland, Ted Krauskopf

Kentucky Grazing Conference

No abstract provided.

Cover Crops/Annuals And Grazing, Roger Staff

Kentucky Grazing Conference

The use of annual forages (cover crops), both summer and winter, have been utilized for several years. When cover crops first were used to extend the grazing season, it began with one to three species in a mixture. That was before the soil health benefits were being observed and discussed as they are now. There have been a wide variety of planting methods used: airplanes, helicopters, conventional and No-till drills. Some seeding methods is simply broadcast on the soils surface and lightly tilled in or just rained in depending upon the weather. Then we discovered the herbicides and amounts used …