Digital Commons Network^™

Capsid Structure Of Dsrna Fungal Viruses, Daniel Luque, Carlos P. Mata, Nobuhiro Suzuki, Said A. Ghabrial, José R. Castón

Plant Pathology Faculty Publications

Most fungal, double-stranded (ds) RNA viruses lack an extracellular life cycle stage and are transmitted by cytoplasmic interchange. dsRNA mycovirus capsids are based on a 120-subunit T = 1 capsid, with a dimer as the asymmetric unit. These capsids, which remain structurally undisturbed throughout the viral cycle, nevertheless, are dynamic particles involved in the organization of the viral genome and the viral polymerase necessary for RNA synthesis. The atomic structure of the T = 1 capsids of four mycoviruses was resolved: the L-A virus of Saccharomyces cerevisiae (ScV-L-A), Penicillium chrysogenum virus (PcV), Penicillium stoloniferum virus F (PsV-F), and Rosellinia necatrix …

Effects Of Beta Blockers And Ace Inhibitors After Left Ventricular Assist Device Implantation, Gaurang Vaidya, Emma Birks, Jessica Pillarella, Benjamin Salgado, Rajakrishnan Vijayakrishnan, Andrew Lenneman, Mark Slaughter, Dmitry Abramov

The VAD Journal

Purpose: While Beta blockers(BB) and Angiotensin system blockers(ACEinh/ARB) are important components in advanced heart failure therapy, their use after left ventricular assist device (LVAD) implantation remains controversial. Concern has been raised about possible adverse effects of BB on right ventricular(RV) function while tolerance and efficacy/outcome data for ACEinh are lacking. This study aimed to characterize the use of medical therapy post-LVAD implantation and to evaluate its safety and efficacy. Methods: Demographic, clinical and echocardiographic variables of patients implanted with a continuous-flow LVAD between 2012 and 2015 at a single center were retrospectively reviewed. Mortality and heart failure(CHF) hospitalizations were followed …

The Conquest Of Pus -- A History Of Bitumen, Creosote And Carbolic Acid, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

In the Western world from antiquity on, open wounds were treated topically with petroleum-derived substances, such as bitumen, asphalt, pitch, and tar. The immediate aim was to stifle bleeding and ease pain but a potential benefit was preventing local corruption with pus formation. In the early 19th century, creosote was recovered from bitumen and found to reduce suppuration. Carbolic acid was later isolated from creosote and recognized as an underlying active agent. In the 1860s, carbolic acid was first employed by Jules Lemaire to treat local skin infections and later by Joseph Lister to prevent the suppuration in compound fractures. …

Does Transcranial Direct Current Stimulation To The Prefrontal Cortex Affect Social Behavior? A Meta-Analysis, Sarah Beth Bell, Nathan Dewall

Psychology Faculty Publications

This meta-analysis (k = 48, N = 2196) examined the effect of transcranial direct current brain stimulation (tDCS) applied to the prefrontal cortex on a variety of social behaviors, including aggression, overeating, impulsivity, bias, honesty, and risk-taking. tDCS showed an overall significant effect on reducing undesirable behaviors, with an average effect size of d = −0.20. tDCS was most effective at reducing risk-taking behavior, bias, and overeating. tDCS did not affect aggression, impulsivity, or dishonesty. We examined moderators such as brain region of interest, online vs offline stimulation, within- vs between-subjects designs, dose, and duration, but none showed significant …

Lasix Lessons Learned: Science Confirms What American Horsemen Knew 50 Years Ago, Clara Fenger, Steve Selway, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

No abstract provided.

New Market Opportunities And Consumer Heterogeneity In The U.S. Organic Food Market, Gwanseon Kim, Jun Ho Seok, Tyler B. Mark

Agricultural Economics Faculty Publications

This paper investigates what factors and characteristics of organic consumers affect annual organic food expenditure by using Nielsen’s consumer panel dataset from 2010 to 2014. To be specific, this paper explores new marketing opportunities by investigating organic consumer heterogeneity in different household income levels by utilizing the multilevel model. Findings in this study will contribute to the previous and existing literature in three-folds. First, we find that the organic consumers are more heterogeneous in the high-level of income groups (approximately above $60,000), as well as the low-income households between $35,000 and $45,000. This finding demonstrates that the income levels above …

Near-Infrared Spectroscopy Used To Predict Soybean Seed Germination And Vigour, Maythem Al-Amery, Robert L. Geneve, Mauricio F. Sanches, Paul R. Armstrong, Elizabeth B. Maghirang, Chad Lee, Roberval D. Vieira, David F. Hildebrand

Horticulture Faculty Publications

Rapid, non-destructive methods for measuring seed germination and vigour are valuable. Standard germination and seed vigour were determined using 81 soybean seed lots. From these data, seed lots were separated into high and low germinating seed lots as well as high, medium and low vigour seed lots. Near-infrared spectra (950–1650 nm) were collected for training and validation samples for each seed category and used to create partial least squares (PLS) prediction models. For both germination and vigour, qualitative models provided better discrimination of high and low performing seed lots compared with quantitative models. The qualitative germination prediction models correctly identified …

P-Value Histograms: Inference And Diagnostics, Patrick Breheny, Arnold Stromberg, Joshua Lambert

Statistics Faculty Publications

It is increasingly common for experiments in biology and medicine to involve large numbers of hypothesis tests. A natural graphical method for visualizing these tests is to construct a histogram from the p-values of these tests. In this article, we examine the shapes, both regular and irregular, that these histograms can take on, as well as present simple inferential procedures that help to interpret the shapes in terms of diagnosing potential problems with the experiment. We examine potential causes of these problems in detail, and discuss potential remedies. Throughout, examples of irregular-looking p-value histograms are provided and based …

Ubiquitin Regulation: The Histone Modifying Enzyme's Story, Jianlin Wang, Zhaoping Qiu, Yadi Wu

Pharmacology and Nutritional Sciences Faculty Publications

Histone post-translational modifications influence many fundamental cellular events by regulating chromatin structure and gene transcriptional activity. These modifications are highly dynamic and tightly controlled, with many enzymes devoted to the addition and removal of these modifications. Interestingly, these modifying enzymes are themselves fine-tuned and precisely regulated at the level of protein turnover by ubiquitin-proteasomal processing. Here, we focus on recent progress centered on the mechanisms regulating ubiquitination of histone modifying enzymes, including ubiquitin proteasomal degradation and the reverse process of deubiquitination. We will also discuss the potential pathophysiological significance of these processes.

Depression Following A Traumatic Brain Injury: Uncovering Cytokine Dysregulation As A Pathogenic Mechanism, Colleen N. Bodnar, Josh M. Morganti, Adam D. Bachstetter

Spinal Cord and Brain Injury Research Center Faculty Publications

A substantial number of individuals have long-lasting adverse effects from a traumatic brain injury (TBI). Depression is one of these long-term complications that influences many aspects of life. Depression can limit the ability to return to work, and even worsen cognitive function and contribute to dementia. The mechanistic cause for the increased depression risk associated with a TBI remains to be defined. As TBI results in chronic neuroinflammation, and priming of glia to a secondary challenge, the inflammatory theory of depression provides a promising framework for investigating the cause of depression following a TBI. Increases in cytokines similar to those …

Transcriptional Response Of Honey Bee (Apis Mellifera) To Differential Nutritional Status And Nosema Infection, Farida Azzouz-Olden, Arthur G. Hunt, Gloria Degrandi-Hoffman

Plant and Soil Sciences Faculty Publications

Background: Bees are confronting several environmental challenges, including the intermingled effects of malnutrition and disease. Intuitively, pollen is the healthiest nutritional choice, however, commercial substitutes, such as Bee-Pro and MegaBee, are widely used. Herein we examined how feeding natural and artificial diets shapes transcription in the abdomen of the honey bee, and how transcription shifts in combination with Nosema parasitism.

Results: Gene ontology enrichment revealed that, compared with poor diet (carbohydrates [C]), bees fed pollen (P > C), Bee-Pro (B > C), and MegaBee (M > C) showed a broad upregulation of metabolic processes, especially lipids; however, pollen feeding promoted more functions, and …

Crop Pests And Predators Exhibit Inconsistent Responses To Surrounding Landscape Composition, Daniel S. Karp, Rebecca Chaplin-Kramer, Timothy D. Meehan, Emily A. Martin, Fabrice Declerck, Heather Grab, Claudio Gratton, Lauren Hunt, Ashley E. Larsen, Alejandra Martínez-Salinas, Megan E. O’Rourke, Adrien Rusch, Katja Poveda, Mattias Jonsson, Jay A. Rosenheim, Nancy A. Schellhorn, Teja Tscharntke, Stephen D. Wratten, Wei Zhang, Aaron L. Iverson, Lynn S. Adler, Matthias Albrecht, Audrey Alignier, Gina M. Angelella, Muhammad Zubair Anjum, Jacques Avelino, Péter Batáry, Johannes M. Baveco, Felix J. J. A. Bianchi, Klaus Birkhofer, David J. Gonthier

Entomology Faculty Publications

The idea that noncrop habitat enhances pest control and represents a win–win opportunity to conserve biodiversity and bolster yields has emerged as an agroecological paradigm. However, while noncrop habitat in landscapes surrounding farms sometimes benefits pest predators, natural enemy responses remain heterogeneous across studies and effects on pests are inconclusive. The observed heterogeneity in species responses to noncrop habitat may be biological in origin or could result from variation in how habitat and biocontrol are measured. Here, we use a pest-control database encompassing 132 studies and 6,759 sites worldwide to model natural enemy and pest abundances, predation rates, and crop …

Double-Stranded Rna Binding Protein, Staufen, Is Required For The Initiation Of Rnai In Coleopteran Insects, June-Sun Yoon, Kanakachari Mogilicherla, Dhandapani Gurusamy, Xien Chen, Shankar C. R. R. Chereddy, Subba R. Palli

Entomology Faculty Publications

RNA interference (RNAi) is being used to develop methods to control pests and disease vectors. RNAi is robust and systemic in coleopteran insects but is quite variable in other insects. The determinants of efficient RNAi in coleopterans, as well as its potential mechanisms of resistance, are not known. RNAi screen identified a double-stranded RNA binding protein (StaufenC) as a major player in RNAi. StaufenC homologs have been identified in only coleopteran insects. Experiments in two coleopteran insects, Leptinotarsa decemlineata and Tribolium castaneum, showed the requirement of StaufenC for RNAi, especially for processing of double-stranded RNA (dsRNA) to small interfering …

Aged Murine Hematopoietic Stem Cells Drive Aging-Associate Immune Remodeling, Hanna Leins, Medhanie Mulaw, Karina Eiwen, Vadim Sakk, Ying Liang, Michael Denkinger, Hartmut Geiger, Reinhold Schirmbeck

Toxicology and Cancer Biology Faculty Publications

Aging-associated remodeling of the immune system impairs its functional integrity and contributes to increased morbidity and mortality in the elderly. Aging of hematopoietic stem cells (HSCs), from which all cells of the adaptive immune system ultimately originate, might play a crucial role in the remodeling of the aged immune system. We recently reported that aging of HSCs is, in part, driven by elevated activity of the small RhoGTPase Cdc42 and that aged HSCs can be rejuvenated in vitro by inhibition of the elevated Cdc42 activity in aged HSCs with the pharmacological compound CASIN. To study the quality of immune systems …

Structure Of The Mouse Trpc4 Ion Channel, Jingjing Duan, Jian Li, Bo Zeng, Gui-Lan Chen, Xiaogang Peng, Yixing Zhang, Jianbin Wang, David E. Clapham, Zongli Li, Jin Zhang

Molecular and Cellular Biochemistry Faculty Publications

Members of the transient receptor potential (TRP) ion channels conduct cations into cells. They mediate functions ranging from neuronally mediated hot and cold sensation to intracellular organellar and primary ciliary signaling. Here we report a cryo-electron microscopy (cryo-EM) structure of TRPC4 in its unliganded (apo) state to an overall resolution of 3.3 Å. The structure reveals a unique architecture with a long pore loop stabilized by a disulfide bond. Beyond the shared tetrameric six-transmembrane fold, the TRPC4 structure deviates from other TRP channels with a unique cytosolic domain. This unique cytosolic N-terminal domain forms extensive aromatic contacts with the TRP …

Quantifying Plant Soluble Protein And Digestible Carbohydrate Content, Using Corn (Zea Mays) As An Exemplar, Carrie A. Deans, Gregory A. Sword, Paul A. Lenhart, Eric Burkness, William D. Hutchison, Spencer T. Behmer

Entomology Faculty Publications

Elemental data are commonly used to infer plant quality as a resource to herbivores. However, the ubiquity of carbon in biomolecules, the presence of nitrogen-containing plant defensive compounds, and variation in species-specific correlations between nitrogen and plant protein content all limit the accuracy of these inferences. Additionally, research focused on plant and/or herbivore physiology require a level of accuracy that is not achieved using generalized correlations. The methods presented here offer researchers a clear and rapid protocol for directly measuring plant soluble proteins and digestible carbohydrates, the two plant macronutrients most closely tied to animal physiological performance. The protocols combine …

Bee Attractiveness Data, Bernadette Maria Mach, Daniel A. Potter

Entomology Research Data

Urban and suburban landscapes can be refuges for biodiversity of bees and other pollinators. Public awareness of declining pollinator populations has increased interest in growing plants that provide floral resources for bees. Various publications and websites list “bee-friendly” plants, but such lists are rarely based on empirical data, nor do they emphasize flowering trees and shrubs, which are a major component of urban landscapes. We quantified bee visitation to 72 species of flowering woody landscape plants across 373 urban and suburban sites in Kentucky and southern Ohio, USA, sampling and identifying the bee assemblages associated with 45 of the most …

Bee Assemblages Data, Bernadette Maria Mach, Daniel A. Potter

Entomology Research Data

Urban and suburban landscapes can be refuges for biodiversity of bees and other pollinators. Public awareness of declining pollinator populations has increased interest in growing plants that provide floral resources for bees. Various publications and websites list “bee-friendly” plants, but such lists are rarely based on empirical data, nor do they emphasize flowering trees and shrubs, which are a major component of urban landscapes. We quantified bee visitation to 72 species of flowering woody landscape plants across 373 urban and suburban sites in Kentucky and southern Ohio, USA, sampling and identifying the bee assemblages associated with 45 of the most …

Evaluation Of Roadway Lighting Practices, Brian K. Howell, William Nicholas Staats, Austin William Obenauf, Jerry G. Pigman

Kentucky Transportation Center Research Report

Adequate roadway lighting allows better driver visibility during nighttime conditions. Research studies show that lighted roadways on average experience 28 percent fewer vehicles crashes on all roadway types. Most state DOTs have historically used High-Pressure Sodium (HPS) lights for their roadside lighting programs due to their wide availability and relatively low purchase costs. However, the short lifespan of HPS results in frequent replacement, leading to high life cycle costs. Light-Emitting Diode (LED) lights consume less energy, demonstrate improved performance, and require less overall maintenance due to their longer lifespans. Over time, this translates into maintenance cost savings for stateDOTs. In …

Overexpression Of Cyb5r3 And Nqo1, Two Nad+-Producing Enzymes, Mimics Aspects Of Caloric Restriction, Alberto Diaz-Ruiz, Michael Lanasa, Joseph Garcia, Hector Mora, Frances Fan, Alejandro Martin-Montalvo, Andrea Di Francesco, Miguel Calvo-Rubio, Andrea Salvador-Pascual, Miguel A. Aon, Kenneth W. Fishbein, Kevin J. Pearson, Jose Manuel Villalba, Placido Navas, Michel Bernier, Rafael De Cabo

Pharmacology and Nutritional Sciences Faculty Publications

Calorie restriction (CR) is one of the most robust means to improve health and survival in model organisms. CR imposes a metabolic program that leads to increased stress resistance and delayed onset of chronic diseases, including cancer. In rodents, CR induces the upregulation of two NADH‐dehydrogenases, namely NAD(P)H:quinone oxidoreductase 1 (Nqo1) and cytochrome b₅ reductase 3 (Cyb5r3), which provide electrons for energy metabolism. It has been proposed that this upregulation may be responsible for some of the beneficial effects of CR, and defects in their activity are linked to aging and several age‐associated diseases. However, …

Rna Binding Proteins Co-Localize With Small Tau Inclusions In Tauopathy, Brandon F. Maziuk, Daniel J. Apicco, Anna Lourdes Cruz, Lulu Jiang, Peter E. A. Ash, Edroaldo Lummertz De Rocha, Cheng Zhang, Wai Haung Yu, John Leszyk, Jose F. Abisambra, Hu Li, Benjamin Wolozin

Sanders-Brown Center on Aging Faculty Publications

The development of insoluble, intracellular neurofibrillary tangles composed of the microtubule-associated protein tau is a defining feature of tauopathies, including Alzheimer’s disease (AD). Accumulating evidence suggests that tau pathology co-localizes with RNA binding proteins (RBPs) that are known markers for stress granules (SGs). Here we used proteomics to determine how the network of tau binding proteins changes with disease in the rTg4510 mouse, and then followed up with immunohistochemistry to identify RNA binding proteins that co-localize with tau pathology. The tau interactome networks revealed striking disease-related changes in interactions between tau and a multiple RBPs, and biochemical fractionation studies demonstrated …

Managing Herbicide Resistance: Listening To The Perspectives Of Practitioners. Procedures For Conducting Listening Sessions And An Evaluation Of The Process, Jill Schroeder, Michael Barrett, David R. Shaw, Amy B. Asmus, Harold Coble, David Ervin, Raymond A. Jussaume Jr., Micheal D. K. Owen, Ian Burke, Cody F. Creech, A. Stanley Culpepper, William S. Curran, Darrin M. Dodds, Todd A. Gaines, Jeffrey L. Gunsolus, Bradley D. Hanson, Prashant Jha, Annie E. Klodd, Andrew R. Kniss, Ramon G. Leon, Sandra Mcdonald, Don W. Morishita, Brian J. Schutte, Christy L. Sprague, Phillip W. Stahlman, Larry E. Steckel, Mark J. Vangessel

Plant and Soil Sciences Faculty Publications

Seven half-day regional listening sessions were held between December 2016 and April 2017 with groups of diverse stakeholders on the issues and potential solutions for herbicide-resistance management. The objective of the listening sessions was to connect with stakeholders and hear their challenges and recommendations for addressing herbicide resistance. The coordinating team hired Strategic Conservation Solutions, LLC, to facilitate all the sessions. They and the coordinating team used in-person meetings, teleconferences, and email to communicate and coordinate the activities leading up to each regional listening session. The agenda was the same across all sessions and included small-group discussions followed by reporting …

Genome-Wide Atlas Of Alternative Polyadenylation In The Forage Legume Red Clover, Manohar Chakrabarti, Randy D. Dinkins, Arthur G. Hunt

Plant and Soil Sciences Faculty Publications

Studies on prevalence and significance of alternative polyadenylation (APA) in plants have been so far limited mostly to the model plants. Here, a genome-wide analysis of APA was carried out in different tissue types in the non-model forage legume red clover (Trifolium pratense L). A profile of poly(A) sites in different tissue types was generated using so-called ‘poly(A)-tag sequencing’ (PATseq) approach. Our analysis revealed tissue-wise dynamics of usage of poly(A) sites located at different genomic locations. We also identified poly(A) sites and underlying genes displaying APA in different tissues. Functional categories enriched in groups of genes manifesting APA between …

Horse Y Chromosome Assembly Displays Unique Evolutionary Features And Putative Stallion Fertility Genes, Jan E. Janečka, Brian W. Davis, Sharmila Ghosh, Nandina Paria, Pranab J. Das, Ludovic Orlando, Mikkel Schubert, Martin K. Nielsen, Tom A. E. Stout, Wesley Brashear, Gang Li, Charles D. Johnson, Richard P. Metz, Al Muatasim Al Zadjali, Charles C. Love, Dickson D. Varner, Daniel W. Bellott, William J. Murphy, Bhanu P. Chowdhary, Terje Raudsepp

Veterinary Science Faculty Publications

Dynamic evolutionary processes and complex structure make the Y chromosome among the most diverse and least understood regions in mammalian genomes. Here, we present an annotated assembly of the male specific region of the horse Y chromosome (eMSY), representing the first comprehensive Y assembly in odd-toed ungulates. The eMSY comprises single-copy, equine specific multi-copy, PAR transposed, and novel ampliconic sequence classes. The eMSY gene density approaches that of autosomes with the highest number of retained X–Y gametologs recorded in eutherians, in addition to novel Y-born and transposed genes. Horse, donkey and mule testis RNAseq reveals several candidate genes for stallion …

Neuroimaging Biomarkers Of Mtor Inhibition On Vascular And Metabolic Functions In Aging Brain And Alzheimer’S Disease, Jennifer Lee, Lucille M. Yanckello, David Ma, Jared D. Hoffman, Ishita Parikh, Scott Thalman, Bjoern Bauer, Anika M. S. Hartz, Fahmeed Hyder, Ai-Ling Lin

Pharmacology and Nutritional Sciences Faculty Publications

The mechanistic target of rapamycin (mTOR) is a nutrient sensor of eukaryotic cells. Inhibition of mechanistic mTOR signaling can increase life and health span in various species via interventions that include rapamycin and caloric restriction (CR). In the central nervous system, mTOR inhibition demonstrates neuroprotective patterns in aging and Alzheimer’s disease (AD) by preserving mitochondrial function and reducing amyloid beta retention. However, the effects of mTOR inhibition for in vivo brain physiology remain largely unknown. Here, we review recent findings of in vivo metabolic and vascular measures using non-invasive, multimodal neuroimaging methods in rodent models for brain aging and AD. …

Point-Of-Sale Specific Willingness To Pay For Quality-Differentiated Beef, Kar Ho Lim, Michael Vassalos, Michael R. Reed

Agricultural Economics Faculty Publications

Despite the growing interest of producers and consumers toward grass-fed, local, and organic beef, the supply chain for these products to reach consumers is not always clear-cut. Among the available options are direct-to-consumers and the conventional food supply chain. Although consumers may pay a premium for beef differentiated by quality attributes, the willingness to pay (WTP) difference across point-of-sales is unclear. In this study, we contrast the WTPs for conventional, grass-fed, local, and organic beef by brick-and-mortar supermarkets (B&Ms), farmers’ markets, and via online stores. We conduct a choice experiment with a nationwide online sample of American consumers. The findings …

Doxorubicin-Induced Elevated Oxidative Stress And Neurochemical Alterations In Brain And Cognitive Decline: Protection By Mesna And Insights Into Mechanisms Of Chemotherapy-Induced Cognitive Impairment ("Chemobrain"), Jeriel T. R. Keeney, Xiaojia Ren, Govind Warrier, Teresa Noel, David K. Powell, Jennifer M. Brelsfoard, Rukhsana Sultana, Kathryn E. Saatman, Daret K. St. Clair, D. Allan Butterfield

Chemistry Faculty Publications

Chemotherapy-induced cognitive impairment (CICI) is now widely recognized as a real and too common complication of cancer chemotherapy experienced by an ever-growing number of cancer survivors. Previously, we reported that doxorubicin (Dox), a prototypical reactive oxygen species (ROS)-producing anti-cancer drug, results in oxidation of plasma proteins, including apolipoprotein A-I (ApoA-I) leading to tumor necrosis factor-alpha (TNF-α)-mediated oxidative stress in plasma and brain. We also reported that co-administration of the antioxidant drug, 2-mercaptoethane sulfonate sodium (MESNA), prevents Dox-induced protein oxidation and subsequent TNF-α elevation in plasma. In this study, we measured oxidative stress in both brain and plasma of Dox-treated mice …

Azithromycin Therapy Reduces Cardiac Inflammation And Mitigates Adverse Cardiac Remodeling After Myocardial Infarction: Potential Therapeutic Targets In Ischemic Heart Disease, Ahmed Al-Darraji, Dalia Haydar, Lakshman Chelvarajan, Himi Tripathi, Bryana R. Levitan, Erhe Gao, Vincent J. Venditto, John C. Gensel, David James Feola, Ahmed Abdel-Latif

Gill Heart & Vascular Institute Faculty Publications

Introduction

Acute myocardial infarction (MI) is a primary cause of worldwide morbidity and mortality. Macrophages are fundamental components of post-MI inflammation. Pro-inflammatory macrophages can lead to adverse cardiac remodeling and heart failure while anti-inflammatory/reparative macrophages enhance tissue healing. Shifting the balance between pro-inflammatory and reparative macrophages post-MI is a novel therapeutic strategy. Azithromycin (AZM), a commonly used macrolide antibiotic, polarizes macrophages towards the anti-inflammatory phenotype, as shown in animal and human studies. We hypothesized that AZM modulates post-MI inflammation and improves cardiac recovery.

Methods and results

Male WT mice (C57BL/6, 6–8 weeks old) were treated with either oral AZM (160 …

Ca2+, Astrocyte Activation And Calcineurin/Nfat Signaling In Age-Related Neurodegenerative Diseases, Pradoldej Sompol, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

Mounting evidence supports a fundamental role for Ca²⁺ dysregulation in astrocyte activation. Though the activated astrocyte phenotype is complex, cell-type targeting approaches have revealed a number of detrimental roles of activated astrocytes involving neuroinflammation, release of synaptotoxic factors and loss of glutamate regulation. Work from our lab and others has suggested that the Ca²⁺/calmodulin dependent protein phosphatase, calcineurin (CN), provides a critical link between Ca²⁺ dysregulation and the activated astrocyte phenotype. A proteolyzed, hyperactivated form of CN appears at high levels in activated astrocytes in both human tissue and rodent tissue around regions of amyloid and …

High-Density Lipoprotein Inhibits Serum Amyloid A-Mediated Reactive Oxygen Species Generation And Nlrp3 Inflammasome Activation, Preetha Shridas, Maria C. De Beer, Nancy R. Webb

Internal Medicine Faculty Publications

Serum amyloid A (SAA) is a high-density apolipoprotein whose plasma levels can increase more than 1000-fold during a severe acute-phase inflammatory response and are more modestly elevated in chronic inflammation. SAA is thought to play important roles in innate immunity, but its biological activities have not been completely delineated. We previously reported that SAA deficiency protects mice from developing abdominal aortic aneurysms (AAAs) induced by chronic angiotensin II (AngII) infusion. Here, we report that SAA is required for AngII-induced increases in interleukin-1β (IL-1β), a potent proinflammatory cytokine that is tightly controlled by the Nod-like receptor protein 3 (NLRP3) inflammasome and …