Digital Commons Network^™

The Nuts And Bolts Of The Platelet Release Reaction, Smita Joshi, Sidney W. Whiteheart

Molecular and Cellular Biochemistry Faculty Publications

Secretion is essential to many of the roles that platelets play in the vasculature, e.g., thrombosis, angiogenesis, and inflammation, enabling platelets to modulate the microenvironment at sites of vascular lesions with a myriad of bioactive molecules stored in their granules. Past studies demonstrate that granule cargo release is mediated by Soluble NSF Attachment Protein Receptor (SNARE) proteins, which are required for granule-plasma membrane fusion. Several SNARE regulators, which control when, where, and how the SNAREs interact, have been identified in platelets. Additionally, platelet SNAREs are controlled by post-translational modifications, e.g., phosphorylation and acylation. Although there have been many …

Proteasome Inhibitors, Kyung Bo Kim, Venod Kasam, Wooin Lee, Dong-Eun Kim, Zachary Miller, Chang-Guo Zhan, Do-Min Lee

Pharmaceutical Sciences Faculty Patents

To see this patent's abstract, please download it.

Current And Emerging Uses Of Statins In Clinical Therapeutics: A Review, Jonathan T. Davies, Spencer F. Delfino, Chad E. Feinberg, Meghan F. Johnson, Veronica L. Nappi, Joshua T. Olinger, Anthony P. Schwab, Hollie I. Swanson

Pharmacology and Nutritional Sciences Faculty Publications

Statins, a class of cholesterol-lowering medications that inhibit 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, are commonly administered to treat atherosclerotic cardiovascular disease. Statin use may expand considerably given its potential for treating an array of cholesterol-independent diseases. However, the lack of conclusive evidence supporting these emerging therapeutic uses of statins brings to the fore a number of unanswered questions including uncertainties regarding patient-to-patient variability in response to statins, the most appropriate statin to be used for the desired effect, and the efficacy of statins in treating cholesterol-independent diseases. In this review, the adverse effects, costs, and drug–drug and drug–food interactions associated with statin …

Genome Of The Asian Longhorned Beetle (Anoplophora Glabripennis), A Globally Significant Invasive Species, Reveals Key Functional And Evolutionary Innovations At The Beetle-Plant Interface, Duane D. Mckenna, Erin D. Scully, Yannick Pauchet, Kelli Hoover, Roy Kirsch, Scott M. Geib, Robert F. Mitchell, Robert M. Waterhouse, Seung-Joon Ahn, Deanna Arsala, Joshua B. Benoit, Heath Blackmon, Tiffany Bledsoe, Julia H. Bowsher, André Busch, Bernarda Calla, Hsu Chao, Anna K. Childers, Christopher Childers, Dave J. Clarke, Lorna Cohen, Jeffery P. Demuth, Huyen Dinh, Harshavardhan Doddapaneni, Amanda Dolan, Jian J. Duan, Shannon Dugan, Markus Friedrich, Karl M. Glastad, Michael A. D. Goodisman, Stephanie Haddad, Yi Han, Daniel S. T. Hughes, Panagiotis Ioannidis, J. Spencer Johnston, Jeffery W. Jones, Leslie A. Kuhn, David R. Lance, Chien-Yueh Lee, Sandra L. Lee, Han Lin, Jeremy A. Lynch, Armin P. Moczek, Shwetha C. Murali, Donna M. Muzny, David R. Nelson, Subba R. Palli, Kristen A. Panfilio, Dan Pers, Monica F. Poelchau, Honghu Quan, Jiaxin Qu, Ann M. Ray, Joseph P. Rinehart, Hugh M. Robertson, Richard Roehrdanz, Andrew J. Rosendale, Seunggwan Shin, Christian Silva, Alex S. Torson, Iris M. Vargas Jentzsch, John H. Werren, Kim C. Worley, George Yocum, Evgeny M. Zdobnov, Richard A. Gibbs, Stephen Richards

Entomology Faculty Publications

Background: Relatively little is known about the genomic basis and evolution of wood-feeding in beetles. We undertook genome sequencing and annotation, gene expression assays, studies of plant cell wall degrading enzymes, and other functional and comparative studies of the Asian longhorned beetle, Anoplophora glabripennis, a globally significant invasive species capable of inflicting severe feeding damage on many important tree species. Complementary studies of genes encoding enzymes involved in digestion of woody plant tissues or detoxification of plant allelochemicals were undertaken with the genomes of 14 additional insects, including the newly sequenced emerald ash borer and bull-headed dung beetle.

Results: …

Caloric Restriction Preserves Memory And Reduces Anxiety Of Aging Mice With Early Enhancement Of Neurovascular Functions, Ishita Parikh, Janet Guo, Kai-Hsiang Chuang, Yu Zhong, Ralf G. Rempe, Jared D. Hoffman, Rachel Armstrong, Björn Bauer, Anika M. S. Hartz, Ai-Ling Lin

Sanders-Brown Center on Aging Faculty Publications

Neurovascular integrity plays an important role in protecting cognitive and mental health in aging. Lifestyle interventions that sustain neurovascular integrity may thus be critical on preserving brain functions in aging and reducing the risk for age-related neurodegenerative disorders. Here we show that caloric restriction (CR) had an early effect on neurovascular enhancements, and played a critical role in preserving vascular, cognitive and mental health in aging. In particular, we found that CR significantly enhanced cerebral blood flow (CBF) and blood-brain barrier function in young mice at 5-6 months of age. The neurovascular enhancements were associated with reduced mammalian target of …

Method And System For Producing Triterpenes, Joe Chappell, Thomas D. Niehaus, Shigeru Okada, Timothy P. Devarenne, David Watt

Pharmaceutical Sciences Faculty Patents

A method and system are provided for the production of triterpene including methylated triterpenes. The method and system include isolated nucleic acid sequences encoding triterpene methyltransferases such as triterpene methyltransferases 1, 2, 3. Advantageously, the method and system includes transgenic plant cells via an expression vector for triterpene methyltransferase and optionally various triterpene synthase and prenyltransferase all with tags directing these enzymes to the chloroplast of the transgenic plant cells for using the chloroplast methyl erythritol phosphate (MEP) pathway in the triterpene biogenesis.

Selection Of Reference Genes For Rt-Qpcr Analysis In Coccinella Septempunctata To Assess Un-Intended Effects Of Rnai Transgenic Plants, Chunxiao Yang, Evan L. Preisser, Hongjun Zhang, Yong Liu, Liangying Dai, Huipeng Pan, Xuguo Zhou

Entomology Faculty Publications

The development of genetically engineered plants that employ RNA interference (RNAi) to suppress invertebrate pests opens up new avenues for insect control. While this biotechnology shows tremendous promise, the potential for both non-target and off-target impacts, which likely manifest via altered mRNA expression in the exposed organisms, remains a major concern. One powerful tool for the analysis of these un-intended effects is reverse transcriptase-quantitative polymerase chain reaction, a technique for quantifying gene expression using a suite of reference genes for normalization. The seven-spotted ladybeetle Coccinella septempunctata, a commonly used predator in both classical and augmentative biological controls, is a …

Methods And Systems For Prognosis And Diagnosis Of Brain Damage, Mark A. Lovell, Bert C. Lynn, Melissa A. Bradley-Whitman

Sanders-Brown Center on Aging Faculty Patents

The presently-disclosed subject matter includes methods and devices for diagnosing, prognosing, and treating brain damage in a subject, including brain damage caused by stroke or a traumatic brain injury (TBI). The methods can comprise providing a sample obtained from the subject, exposing the sample to an antibody selective for a visinin-like protein, detecting the presence of a complex that includes the antibody and the visinin-like protein, and diagnosing and/or prognosing the subject as having brain damage if there is the presence of the complex. Embodied methods can also comprise administering a treatment for brain damage if the subject includes the …

Forage News [2016-11], Department Of Plant And Soil Sciences, University Of Kentucky

Forage News

• The New Face of Forage News
• Changes to FSA Acreage Reporting Dates for 2017
• Heart of America Grazing Conference to be held in Quincy, IL January 18-19
• Forage News Quote of the Month: "Wasted Hay Means Wasted Money"
• Overseeding Small Grains into Pastures or Hayfields
• AFGC Annual Meeting - January 22-24, 2017
• Somerset KY Hosts Successful Kentucky Grazing Conference
• Featured Publication: Taking Soil Test Samples - AGR-16
• Dairy Market Continues to Struggle

Modern Politics And The Passions, David Bradshaw

Institute for the Study of Free Enterprise Working Papers

Why is our society today so sharply divided—politically, socially and morally?

Professor Bradshaw argues that the answer can be found in two of the foundational philosophers of the modern era, John Locke and Jean-Jacques Rousseau. Although they are sharply opposed in many ways, they share some common features that set the pattern for modern politics.

The Life Cycle Stages Of Pneumocystis Murina Have Opposing Effects On The Immune Response To This Opportunistic Fungal Pathogen, Heather M. Evans, Grady L. Bryant Iii, Beth A. Garvy

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The cell wall β-glucans of Pneumocystis cysts have been shown to stimulate immune responses in lung epithelial cells, dendritic cells, and alveolar macrophages. Little is known about how the trophic life forms, which do not have a fungal cell wall, interact with these innate immune cells. Here we report differences in the responses of both neonatal and adult mice to the trophic and cystic life cycle stages of Pneumocystis murina. The adult and neonatal immune responses to infection with Pneumocystis murina trophic forms were less robust than the responses to infection with a physiologically normal mixture of cysts and …

Citations Increase With Manuscript Length, Author Number, And References Cited In Ecology Journals, Charles W. Fox, C. E. Timothy Paine, Boris Sauterey

Entomology Faculty Publications

Most top impact factor ecology journals indicate a preference or requirement for short manuscripts; some state clearly defined word limits, whereas others indicate a preference for more concise papers. Yet evidence from a variety of academic fields indicates that within journals longer papers are both more positively reviewed by referees and more highly cited. We examine the relationship between citations received and manuscript length, number of authors, and number of references cited for papers published in 32 ecology journals between 2009 and 2012. We find that longer papers, those with more authors, and those that cite more references are cited …

Building Viral Replication Organelles: Close Encounters Of The Membrane Types, Peter D. Nagy, Jeroen R. P. M. Strating, Frank J. M. Van Kuppeveld

Plant Pathology Faculty Publications

Positive-strand (+)RNA viruses are important and emerging pathogens of humans, animals, and plants. Upon infection, they induce the formation of specialized membranous replication organelles with unique lipid composition to facilitate robust virus replication. In this article, the authors discuss the proviral role of virus-induced membrane contact sites (vMCSs). The emerging picture is that vMCSs channel lipids to viral membranes and tune the lipid composition for optimal generation and functioning of replication organelles.

Two Complete Mitochondrial Genomes From Praticolella Mexicana Perez, 2011 (Polygyridae) And Gene Order Evolution In Helicoidea (Mollusca, Gastropoda), Russell L. Minton, Marco A. Martinez Cruz, Mark L. Farman, Kathryn E. Perez

Plant Pathology Faculty Publications

Helicoidea is a diverse group of land snails with a global distribution. While much is known regarding the relationships of helicoid taxa, comparatively little is known about the evolution of the mitochondrial genome in the superfamily. We sequenced two complete mitochondrial genomes from Praticolella mexicana Perez, 2011 representing the first such data from the helicoid family Polygyridae, and used them in an evolutionary analysis of mitogenomic gene order. We found the mitochondrial genome of P. mexicana to be 14,008 bp in size, possessing the typical 37 metazoan genes. Multiple alternate stop codons are used, as are incomplete stop codons. Mitogenome …

P70s6k1 (S6k1)-Mediated Phosphorylation Regulates Phosphatidylinositol 4-Phosphate 5-Kinase Type I Γ Degradation And Cell Invasion, Naser Jafari, Qiaodan Zheng, Liqing Li, Wei Li, Lei Qi, Jianyong Xiao, Tianyan Gao, Cai Huang

Markey Cancer Center Faculty Publications

Phosphatidylinositol 4-phosphate 5-kinase type I γ (PIPKIγ90) ubiquitination and subsequent degradation regulate focal adhesion assembly, cell migration, and invasion. However, it is unknown how upstream signals control PIPKIγ90 ubiquitination or degradation. Here we show that p70S6K1 (S6K1), a downstream target of mechanistic target of rapamycin (mTOR), phosphorylates PIPKIγ90 at Thr-553 and Ser-555 and that S6K1-mediated PIPKIγ90 phosphorylation is essential for cell migration and invasion. Moreover, PIPKIγ90 phosphorylation is required for the development of focal adhesions and invadopodia, key machineries for cell migration and invasion. Surprisingly, substitution of Thr-553 and Ser-555 …

Age-Related Effect Of Viral-Induced Wheezing In Severe Prematurity, Geovanny F. Perez, Amisha Jain, Bassem Kurdi, Rosemary Megalaa, Krishna Pancham, Shehlanoor Huseni, Natalia Isaza, Carlos E. Rodriguez-Martinez, Mary C. Rose, Dinesh Pillai, Gustavo Nino

Pediatrics Faculty Publications

Abstract: Premature children are prone to severe viral respiratory infections in early life, but the age at which susceptibility peaks and disappears for each pathogen is unclear. Methods: A retrospective analysis was performed of the age distribution and clinical features of acute viral respiratory infections in full-term and premature children, aged zero to seven years. Results: The study comprised of a total of 630 hospitalizations (n = 580 children). Sixty-seven percent of these hospitalizations occurred in children born full-term (> 37 weeks), 12% in preterm (32–37 weeks) and 21% in severely premature children (< 32 weeks). The most common viruses identified were rhinovirus (RV; 60%) and respiratory syncytial virus (RSV; 17%). Age-distribution analysis of each virus identified that severely premature children had a higher relative frequency of RV and RSV in their first three years, relative to preterm or full-term children. Additionally, the probability of RV- or RSV-induced wheezing was higher overall in severely premature children less than three years old. Conclusions: Our results indicate that the …

Juvenile Hormone Regulation Of Female Reproduction In The Common Bed Bug, Cimex Lectularius, Hemant Gujar, Subba Reddy Palli

Entomology Faculty Publications

To begin studies on reproduction in common bed bug, Cimex lectularius, we identified three genes coding for vitellogenin (Vg, a protein required for the reproductive success of insects) and studied their hormonal regulation. RNA interference studied showed that expression of Vg3 gene in the adult females is a prerequisite for successful completion of embryogenesis in the eggs laid by them. Juvenile hormone (JH) receptor, Methoprene-tolerant (Met), steroid receptor coactivator (SRC) and GATAa but not ecdysone receptor (EcR) or its partner, ultraspiracle (USP) are required for expression of Vg genes. Feeding and mating working through Vg, Met, SRC, EcR, and …

Plant Expression Of Cocaine Hydrolase-Fc Fusion Protein For Treatment Of Cocaine Abuse, Guojun Wang, Ting Zhang, Haifeng Huang, Shurong Hou, Xiabin Chen, Fang Zheng, Chang-Guo Zhan

Molecular Modeling and Biopharmaceutical Center Faculty Publications

BACKGROUND: A recently reported cocaine hydrolase (CocH3) fused with fragment crystallizable (Fc) region of human immunoglobulin G1, denoted as CocH3-Fc, is known as a promising therapeutic candidate for the treatment of cocaine overdose and addiction. A challenge for practical therapeutic use of this enzyme exists in the large-scale protein production and, therefore, it is interesting to identify a low-cost and feasible, sustainable source of CocH3-Fc production.

RESULTS: CocH3-Fc was transiently expressed in plant Nicotiana benthamiana leaves. The plant-expressed protein, denoted as pCocH3-Fc, was as active as that expressed in mammalian cells both in vitro and in vivo. However, compared to …

Pleckstrin Homology (Ph) Domain Leucine-Rich Repeat Protein Phosphatase Controls Cell Polarity By Negatively Regulating The Activity Of Atypical Protein Kinase C, Xiaopeng Xiong, Xin Li, Yang-An Wen, Tianyan Gao

Markey Cancer Center Faculty Publications

The proper establishment of epithelial polarity allows cells to sense and respond to signals that arise from the microenvironment in a spatiotemporally controlled manner. Atypical PKCs (aPKCs) are implicated as key regulators of epithelial polarity. However, the molecular mechanism underlying the negative regulation of aPKCs remains largely unknown. In this study, we demonstrated that PH domain leucine-rich repeat protein phosphatase (PHLPP), a novel family of Ser/Thr protein phosphatases, plays an important role in regulating epithelial polarity by controlling the phosphorylation of both aPKC isoforms. Altered expression of PHLPP1 or PHLPP2 disrupted polarization of Caco2 cells grown in 3D cell cultures …

Methods For Diagnosing And Treating Alzheimer's Disease (Ad) Using The Molecules That Stabilize Intracellular Calcium (Ca2+) Release, Philip W. Landfield, John C. Gant, Eric M. Blalock, Kuey-Chu Chen, Olivier Thibault, Nada M. Porter

Pharmacology and Nutritional Sciences Faculty Patents

The subject technology relates, in part, to a method of treating Alzheimer's Disease (AD), early-stage AD, elevated risk of AD, mild cognitive impairment (MCI), or other forms of age-related cognitive decline in a subject in need thereof by administering to the subject a molecule that promotes calcium-release stabilization in ryanodine receptors (RyRs) and/or inosital triphosphate receptors (InsP3Rs) in brain cells. Diagnostic methods using calcium-release stabilizing immunophilins, junctophilins or calmodulin are also disclosed.

Methods Of Inhibiting Alu Rna And Therapeutic Uses Thereof, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Patents

The presently-disclosed subject matter includes methods of identifying an Alu RNA inhibitor, and methods and compositions for inhibiting Alu RNA. Methods and compositions can be used for the treatment of geographic atrophy and other conditions of interest.

Sphingosine 1-Phosphate Activation Of Egfr As A Novel Target For Meningitic Escherichia Coli Penetration Of The Blood-Brain Barrier, Xiangru Wang, Ravi Maruvada, Andrew J. Morris, Jun O. Liu, Michael J. Wolfgang, Dong Jae Baek, Robert Bittman, Kwang Sik Kim

Internal Medicine Faculty Publications

Central nervous system (CNS) infection continues to be an important cause of mortality and morbidity, necessitating new approaches for investigating its pathogenesis, prevention and therapy. Escherichia coli is the most common Gram-negative bacillary organism causing meningitis, which develops following penetration of the blood–brain barrier (BBB). By chemical library screening, we identified epidermal growth factor receptor (EGFR) as a contributor to E. coli invasion of the BBB in vitro. Here, we obtained the direct evidence that CNS-infecting E. coli exploited sphingosine 1-phosphate (S1P) for EGFR activation in penetration of the BBB in vitro and in vivo. We …

Functional Value Of Elytra Under Various Stresses In The Red Flour Beetle, Tribolium Castaneum, David M. Linz, Alan W. Hu, Michael I. Sitvarin, Yoshinori Tomoyasu

Entomology Faculty Publications

Coleoptera (beetles) is a massively successful order of insects, distinguished by their evolutionarily modified forewings called elytra. These structures are often presumed to have been a major driving force for the successful radiation of this taxon, by providing beetles with protection against a variety of harsh environmental factors. However, few studies have directly demonstrated the functional significance of the elytra against diverse environmental challenges. Here, we sought to empirically test the function of the elytra using Tribolium castaneum (the red flour beetle) as a model. We tested four categories of stress on the beetles: physical damage to hindwings, predation, desiccation, …

Defining And Targeting Health Disparities In Chronic Obstructive Pulmonary Disease, Roy A. Pleasants, Isaretta L. Riley, David M. Mannino

Preventive Medicine and Environmental Health Faculty Publications

The global burden of chronic obstructive pulmonary disease (COPD) continues to grow in part due to better outcomes in other major diseases and in part because a substantial portion of the worldwide population continues to be exposed to inhalant toxins. However, a disproportionate burden of COPD occurs in people of low socioeconomic status (SES) due to differences in health behaviors, sociopolitical factors, and social and structural environmental exposures. Tobacco use, occupations with exposure to inhalant toxins, and indoor biomass fuel (BF) exposure are more common in low SES populations. Not only does SES affect the risk of developing COPD and …

Beryllium Nitrate Inhibits Fibroblast Migration To Disrupt Epimorphic Regeneration, Adam B. Cook, Ashley W. Seifert

Biology Faculty Publications

Epimorphic regeneration proceeds with or without formation of a blastema, as observed for the limb and skin, respectively. Inhibition of epimorphic regeneration provides a means to interrogate the cellular and molecular mechanisms that regulate it. In this study, we show that exposing amputated limbs to beryllium nitrate disrupts blastema formation and causes severe patterning defects in limb regeneration. In contrast, exposing full-thickness skin wounds to beryllium only causes a delay in skin regeneration. By transplanting full-thickness skin from ubiquitous GFP-expressing axolotls to wild-type hosts, we demonstrate that beryllium inhibits fibroblast migration during limb and skin regeneration in vivo. Moreover, …

Tgf-Β Signaling: New Insights Into Aortic Aneurysms, Sean E. Thatcher

Pharmacology and Nutritional Sciences Faculty Publications

No abstract provided.

Epigenetics Of Lipid Phenotypes, Sergi Sayols-Baixeras, Marguerite R. Irvin, Donna K. Arnett, Roberto Elosua, Stella W. Aslibekyan

Epidemiology and Environmental Health Faculty Publications

Dyslipidemia is a well-established risk factor for cardiovascular disease, the main cause of death worldwide. Blood lipid profiles are patterned by both genetic and environmental factors. In recent years, epigenetics has emerged as a paradigm that unifies these influences. In this review, we have summarized the latest evidence implicating epigenetic mechanisms—DNA methylation, histone modification, and regulation by RNAs—in lipid homeostasis. Key findings have emerged in a number of novel epigenetic loci located in biologically plausible genes (eg, CPT1A, ABCG1, SREBF1, and others), as well as microRNA-33a/b. Evidence from animal and cell culture models suggests a complex interplay …

Forage News [2016-10], Department Of Plant And Soil Sciences, University Of Kentucky

Forage News

• KY Grazing Conference Write Up
• Tribute to a Forage Legend: Warren Thompson
• Frost and Freezes Increase Cyanide Poisoning Risk
• Kentucky Cattlemen Association Presents Forage Specialist Funds at the KFGC Field Day
• Forage News Quote of the Month: "Beware of Emotional Decision" - Russell Hackley
• Fall Nitrogen Boosts Winter Survival and Spring Greenup
• Master Grazer's new Coordinator, Jacob Brandenburg
• Featured Publication: Calculating Carrying Capacity Using Web Soil Survey, AGR-222

Physicochemical Properties Of Engineered Nanomaterials That Influence Their Nervous System Distribution And Effects, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

This critical review examines in vitro and in vivo evidence for the influence of engineered nanomaterial (ENM) physicochemical properties on their distribution into, and effects on, the nervous system. Nervous system applications of ENMs; exposure routes and potential for uptake; the nervous system and its barriers to ENM uptake; and the mechanisms of uptake into the nervous system and overcoming those barriers are summarized. The findings of English-language publications of studies that included at least two variations of an ENM physicochemical property and reported results of their pharmacokinetic and/or pharmacodynamic interaction with the nervous system that differed as a function …

Pharmacology Of Cannabis, Mandakini Sadhir

Pediatrics Faculty Publications

Cannabis has been used for recreational purposes around the world. It is derived from the plant cannabis sativa which has various other compounds known as cannabinoids. Most common form of cannabis used for recreational purpose is marijuana, which is prepared from dried flowering tops and leaves. The primary psychoactive component is delta 9-tetrahydrocannabinol (δ-9THC), which exerts its physiological and psychological effects through its interaction with CB1 and CB2 receptors. Smoking is the most commonly used method with onset of effects within minutes after inhalation. Oral ingestion of cannabis has varied absorption with delayed onset but longer duration of action. Urine …