Digital Commons Network^™

Why Is Intake Reduced When Cattle Are Fed Tall Fescue?, James L. Klotz

Kentucky Alfalfa and Stored Forage Conference

A major problem for the cattle producer that utilizes tall fescue forage is the unrealized or reduced gains in body weight in growing animals. This result has been reproduced across numerous studies evaluating cattle performance on tall fescue (Hoveland et al., 1983; Boling, 1985; Schmidt et al., 1986; Goetsch et al., 1987). Cattle have gained from 30 to 100% less consuming toxic endophyte-infected tall fescue compared to consumption of an endophyte-free tall fescue (Paterson et al., 1995). This effect of reduced gain is a consequence of a fungal endophyte present within the grass that produces toxins called ergot alkaloids. Fungal …

Calcium's Role As Nuanced Modulator Of Cellular Physiology In The Brain, Hilaree N. Frazier, Shaniya Maimaiti, Katie L. Anderson, Lawrence D. Brewer, John C. Gant, Nada M. Porter, Olivier Thibault

Pharmacology and Nutritional Sciences Faculty Publications

Neuroscientists studying normal brain aging, spinal cord injury, Alzheimer’s disease (AD) and other neurodegenerative diseases have focused considerable effort on carefully characterizing intracellular perturbations in calcium dynamics or levels. At the cellular level, calcium is known for controlling life and death and orchestrating most events in between. For many years, intracellular calcium has been recognized as an essential ion associated with nearly all cellular functions from cell growth to degeneration. Often the emphasis is on the negative impact of calcium dysregulation and the typical worse-case-scenario leading inevitably to cell death. However, even high amplitude calcium transients, when executed acutely can …

Dub3 Inhibition Suppresses Breast Cancer Invasion And Metastasis By Promoting Snail1 Degradation, Yadi Wu, Yu Wang, Yiwei Lin, Yajuan Liu, Yifan Wang, Jianhang Jia, Puja Singh, Young-In Chi, Chi Wang, Chenfang Dong, Wei Li, Min Tao, Dana L. Napier, Qiuying Shi, Jiong Deng, B. Mark Evers, Binhua P. Zhou

Pharmacology and Nutritional Sciences Faculty Publications

Snail1, a key transcription factor of epithelial–mesenchymal transition (EMT), is subjected to ubiquitination and degradation, but the mechanism by which Snail1 is stabilized in tumours remains unclear. We identify Dub3 as a bona fide Snail1 deubiquitinase, which interacts with and stabilizes Snail1. Dub3 is overexpressed in breast cancer; knockdown of Dub3 resulted in Snail1 destabilization, suppressed EMT and decreased tumour cell migration, invasion, and metastasis. These effects are rescued by ectopic Snail1 expression. IL-6 also stabilizes Snail1 by inducing Dub3 expression, the specific inhibitor WP1130 binds to Dub3 and inhibits the Dub3-mediating Snail1 stabilization in vitroand in vivo. …

M2 Polarization Of Macrophages Facilitates Arsenic-Induced Cell Transformation Of Lung Epithelial Cells, Jiajun Cui, Wenhua Xu, Jian Chen, Hui Li, Lu Dai, Jacqueline A. Frank, Shaojun Peng, Siying Wang, Gang Chen

Pharmacology and Nutritional Sciences Faculty Publications

The alterations in microenvironment upon chronic arsenic exposure may contribute to arsenic-induced lung carcinogenesis. Immune cells, such as macrophages, play an important role in mediating the microenvironment in the lungs. Macrophages carry out their functions after activation. There are two activation status for macrophages: classical (M1) or alternative (M2); the latter is associated with tumorigenesis. Our previous work showed that long-term arsenic exposure induces transformation of lung epithelial cells. However, the crosstalk between epithelial cells and macrophages upon arsenic exposure has not been investigated. In this study, using a co-culture system in which human lung epithelial cells are cultured with …

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, …

The Molecular Basis Of Talin2'S High Affinity Toward Β1-Integrin, Yaxia Yuan, Liqing Li, Yanyan Zhu, Lei Qi, Latifeh Azizi, Vesa P. Hytönen, Chang-Guo Zhan, Cai Huang

Molecular Modeling and Biopharmaceutical Center Faculty Publications

Talin interacts with β-integrin tails and actin to control integrin activation, thus regulating focal adhesion dynamics and cell migration. There are two talin genes, Tln1 and Tln2, which encode talin1 and talin2, and it is generally believed that talin2 functions redundantly with talin1. However, we show here that talin2 has a higher affinity to β1-integrin tails than talin1. Mutation of talin2 S339 to leucine, which can cause Fifth Finger Camptodactyly, a human genetic disease, completely disrupted its binding to β–integrin tails. Also, substitution of talin1 C336 with Ser enhanced the affinity of talin1, whereas substitution of talin2 S339 with …

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 …

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 …

Using Natural Experiments To Identify The Effects Of Snap On Child And Adult Health, Daniel P. Miller, Taryn W. Morrissey

University of Kentucky Center for Poverty Research Discussion Paper Series

The Supplemental Nutrition Assistance Program (SNAP; formerly known as food stamps) can have important impacts that extend beyond its intended aims to improve food security and nutrition, particularly for health and health care use. This project examined the impact of SNAP receipt and benefit level on the health of adults and children using two natural experiments to address selection bias: 1) state policy variation in SNAP in an instrumental variables (IV) analysis; and, 2) the temporary expansion of SNAP benefits and eligibility provided through the American Recovery and Reinvestment Act (ARRA) in a difference-in-difference (DD) approach. We used restricted data …

Inhibition Of The Integrin/Fak Signaling Axis And C-Myc Synergistically Disrupts Ovarian Cancer Malignancy, B. Xu, Jason R. Lefringhouse, Z. Liu, D. West, Lauren A. Baldwin, C. Ou, L. Chen, Dana L. Napier, Luksana Chaiswing, Lawrence D. Brewer, Daret K. St Clair, Olivier Thibault, John R. Van Nagell, Binhua P. Zhou, R. Drapkin, J.-A. Huang, M. L. Lu, Frederick R. Ueland, X. H. Yang

Pharmacology and Nutritional Sciences Faculty Publications

Integrins, a family of heterodimeric receptors for extracellular matrix, are promising therapeutic targets for ovarian cancer, particularly high-grade serous-type (HGSOC), as they drive tumor cell attachment, migration, proliferation and survival by activating focal adhesion kinase (FAK)-dependent signaling. Owing to the potential off-target effects of FAK inhibitors, disruption of the integrin signaling axis remains to be a challenge. Here, we tackled this barrier by screening for inhibitors being functionally cooperative with small-molecule VS-6063, a phase II FAK inhibitor. From this screening, JQ1, a potent inhibitor of Myc oncogenic network, emerged as the most robust collaborator. Treatment with a combination of VS-6063 …

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 …

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 …

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, …

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 …

Microbial Interactions In The Phyllosphere Increase Plant Performance Under Herbivore Biotic Stress, Muhammad Saleem, Nicole Meckes, Zahida H. Pervaiz, Milton B. Traw

Plant and Soil Sciences Faculty Publications

The phyllosphere supports a tremendous diversity of microbes and other organisms. However, little is known about the colonization and survival of pathogenic and beneficial bacteria alone or together in the phyllosphere across the whole plant life-cycle under herbivory, which hinders our ability to understand the role of phyllosphere bacteria on plant performance. We addressed these questions in experiments using four genetically and biogeographically diverse accessions of Arabidopsis thaliana, three ecologically important bacterial strains (Pseudomonas syringae DC3000, Xanthomonas campestris, both pathogens, and Bacillus cereus, plant beneficial) under common garden conditions that included fungus gnats (Bradysia spp.). …

Moderator Biographies, Heart Of America Grazing Conference

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 …

Mitigating The Challenges Of Grazing Lush, Spring Forages, W. Travis Meteer

Kentucky Grazing Conference

During the winter season most cattle are supplemented with dry forages, grains, and co-products. This ration is balanced and delivered to cattle. Then spring comes along and cattle are put out to grass. While green grass solves a lot of problems associated with winter feeding (manure, pen maintenance, calf health, and labor demands), it can pose nutritional challenges. Lush, spring forage has three major challenges when it comes to meeting cattle nutrition requirements.

Seedhead Suppression In Tall Fescue With Chaparral Herbicide, E. S. Flynn, P. B. Burch

Kentucky Grazing Conference

Tall Fescue (Lolium arundinaceum (Schreb.)) is cool-season perennial grass found in pastures throughout the Eastern US, most commonly in the transition zone. It’s tolerance to extreme temperatures, drought, poor soil fertility, heavy grazing, and pests have made it a reliable forage base for livestock pastures. Released in 1943, ‘KY-31’ tall fescue was quickly adopted by cattle producers and now inhabits an estimated 40 million acres in the US.

Soon after its adoption, cattle producers began to notice a reduction in animal performance and signs that animals were heat stressed following tall fescue consumption. These symptoms were an indication of an …

Fescue Tolerance Testing, Monty Kerley

Kentucky Grazing Conference

Fescue toxicosis is characterized by clinical symptoms such as vasoconstriction, immunosuppression, and poor thermoregulation. Fescue toxins bind to membrane receptors of cells that control constriction of blood through capillaries responsible for heat dissipation. When cattle consume toxic tall fescue, they lose ability to move blood to their skin where heat can be lost to the environment. As they lose this ability they become more prone to heat stress. In the winter, this lack of blood flow leads to other clinical symptoms, such as fescue foot and loss of tail switch, that occur from restricted blood flow.

Research Update: Beef Cattle Management Considerations For Grazing Tall Fescue, Frank Ireland

Kentucky Grazing Conference

It has been reported that 8 million beef cattle graze an estimated 35 million acres of endophyte-infected tall fescue in the United States with the majority of tall fescue being produced in the Midwest and southeastern regions of the United States. In the presence of the endophytic fungus, ergot alkaloids are present that when consumed by beef cattle results in decreased animal performance as measured in reduced weight gains, lower body condition scores, decreased conception rates, rough hair coats and the inability to regulate body temperatures. It has been estimated that this loss in animal performance accounts for a $600 …

Foreword And Conference Information [2017], Matt Bunger

Kentucky Grazing Conference

This is the front matter of the proceedings.

Association Of Body Mass Index With Dna Methylation And Gene Expression In Blood Cells And Relations To Cardiometabolic Disease: A Mendelian Randomization Approach, Michael M. Mendelson, Riccardo E. Marioni, Roby Joehanes, Chunyu Liu, Åsa K. Hedman, Stella Aslibekyan, Ellen W. Demerath, Weihua Guan, Degui Zhi, Chen Yao, Tianxiao Huan, Christine Willinger, Brian Chen, Paul Courchesne, Michael Multhaup, Marguerite R. Irvin, Ariella Cohain, Eric E. Schadt, Megan L. Grove, Jan Bressler, Kari North, Johan Sundström, Stefan Gustafsson, Sonia Shah, Allan F. Mcrae, Sarah E. Harris, Jude Gibson, Paul Redmond, Janie Corley, Lee Murphy, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Background

The link between DNA methylation, obesity, and adiposity-related diseases in the general population remains uncertain.

Methods and Findings

We conducted an association study of body mass index (BMI) and differential methylation for over 400,000 CpGs assayed by microarray in whole-blood-derived DNA from 3,743 participants in the Framingham Heart Study and the Lothian Birth Cohorts, with independent replication in three external cohorts of 4,055 participants. We examined variations in whole blood gene expression and conducted Mendelian randomization analyses to investigate the functional and clinical relevance of the findings. We identified novel and previously reported BMI-related differential methylation at 83 CpGs …

Novel Interconnections In Lipid Metabolism Revealed By Overexpression Of Sphingomyelin Synthase-1, Gergana M. Deevska, Patrick P. Dotson Ii, Alexander A. Karakashian, Giorgis Isaac, Mark Wrona, Samuel B. Kelly, Alfred H. Merrill Jr., Mariana N. Nikolova‑Karakashian

Physiology Faculty Publications

This study investigates the consequences of elevating sphingomyelin synthase 1 (SMS1) activity, which generates the main mammalian sphingolipid, sphingomyelin. HepG2 cells stably transfected with SMS1 (HepG2-SMS1) exhibit elevated enzyme activity in vitro and increased sphingomyelin content (mainly C22:0- and C24:0-sphingomyelin) but lower hexosylceramide (Hex-Cer) levels. HepG2-SMS1 cells have fewer triacylglycerols than controls but similar diacylglycerol acyltransferase activity, triacylglycerol secretion, and mitochondrial function. Treatment with 1 mm palmitate increases de novo ceramide synthesis in both cell lines to a similar degree, causing accumulation of C16:0-ceramide (and some C18:0-, C20:0-, and C22:0-ceramides) as well as C16:0- and C18:0-Hex-Cers. In these experiments, the …

Addendum Guidelines For The Prevention Of Peanut Allergy In The United States: Report Of The National Institute Of Allergy And Infectious Diseases–Sponsored Expert Panel, Alkis Togias, Susan F. Cooper, Maria L. Acebal, Amal Assa'ad, James R. Baker, Lisa A. Beck, Julie Block, Carol Byrd-Bredbenner, Edmond S. Chan, Lawrence F. Eichenfield, David M Fleischer, George J. Fuchs Iii, Glenn T. Furuta, Matthew J. Greenhawt, Ruchi S. Gupta, Michele Habich, Stacie M. Jones, Kari Keaton, Antonella Muraro, Marshall Plaut, Lanny J. Rosenwasser, Daniel Rotrosen, Hugh A. Sampson, Lynda C. Schneider, Scott H. Sicherer, Robert Sidbury, Jonathan Spergel, David R. Stukus, Carina Venter, Joshua A. Boyce

Pediatrics Faculty Publications

Background: Food allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy.

Objectives: Prompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy …

Myogenic Progenitor Cells Control Extracellular Matrix Production By Fibroblasts During Skeletal Muscle Hypertrophy, Christopher S. Fry, Tyler J. Kirby, Kate Kosmac, John J. Mccarthy, Charlotte A. Peterson

Physiology Faculty Publications

Satellite cells, the predominant stem cell population in adult skeletal muscle, are activated in response to hypertrophic stimuli and give rise to myogenic progenitor cells (MPCs) within the extracellular matrix (ECM) that surrounds myofibers. This ECM is composed largely of collagens secreted by interstitial fibrogenic cells, which influence satellite cell activity and muscle repair during hypertrophy and aging. Here we show that MPCs interact with interstitial fibrogenic cells to ensure proper ECM deposition and optimal muscle remodeling in response to hypertrophic stimuli. MPC-dependent ECM remodeling during the first week of a growth stimulus is sufficient to ensure long-term myofiber hypertrophy. …

Increased Ros Production In Non-Polarized Mammary Epithelial Cells Induces Monocyte Infiltration In 3d Culture, Linzhang Li, Jie Chen, Gaofeng Xiong, Daret K. St. Clair, Wei Xu, Ren Xu

Markey Cancer Center Faculty Publications

Loss of epithelial cell polarity promotes cell invasion and cancer dissemination. Therefore, identification of factors that disrupt polarized acinar formation is crucial. Reactive oxygen species (ROS) drive cancer progression and promote inflammation. Here, we show that the non-polarized breast cancer cell line T4-2 generates significantly higher ROS levels than polarized S1 and T4R cells in three-dimensional (3D) culture, accompanied by induction of the nuclear factor κB (NF-κB) pathway and cytokine expression. Minimizing ROS in T4-2 cells with antioxidants reestablished basal polarity and inhibited cell proliferation. Introducing constitutively activated RAC1 disrupted cell polarity and increased ROS levels, indicating that RAC1 is …

Child Age And Gender Differences In Food Security In A Low-Income Inner-City Population, Robert A. Moffitt, David C. Ribar

University of Kentucky Center for Poverty Research Discussion Paper Series

A long literature in economics concerns itself with differential allocations of resources to different children within the family unit. In a study of approximately 1,500 very disadvantaged families with children in Boston, Chicago, and San Antonio from 1999 to 2005, significant differences in levels of food allocation, as measured by an indicator of food “insecurity,” are found across children of different ages and genders. Using answers to unique survey questions for a specific child in the family, food insecurity levels are found to be much higher among older boys and girls than among younger ones, and to be sometimes higher …