Digital Commons Network^™

Two Classes Of Nucleic Acid Translocation Motors: Rotation And Revolution Without Rotation, Peixuan Guo, Ian Grainge, Zhengyi Zhao, Mario Vieweger

Markey Cancer Center Faculty Publications

Biomotors are extensively involved in biological processes including cell mitosis, bacterial binary fission, DNA replication, DNA repair, homologous recombination, Holliday junction resolution, RNA transcription, and viral genome packaging. Traditionally, they were classified into two categories including linear and rotation motors. In 2013, a third class of motor by revolution mechanism without rotation was discovered. In this issue of "Structure and mechanisms of nanomotors in the cells", four comprehensive reviews are published to address the latest advancements of the structure and motion mechanism of a variety of biomotors in archaea, animal viruses, bacteria, and bacteriophages.

Expression Of Peroxiredoxin 1 And 4 Promotes Human Lung Cancer Malignancy, Hong Jiang, Lisha Wu, Murli Mishra, Hedy A. Chawsheen, Qiou Wei

Toxicology and Cancer Biology Faculty Publications

Members of the Peroxiredoxin (Prx) family are major cellular antioxidants that scavenge hydrogen peroxide and play essential roles in oxidative stress and cell signaling. 2-Cys Prxs, including Prx1, 2, 3 and 4, have been indicated in multiple oncogenic signaling pathways and thus may contribute to various processes of cancer development. The significance of 2-Cys Prxs in lung cancer development and their biological function in signal transduction have not been fully investigated. In this study we analyzed the expression of 2-Cys Prxs in lung cancer, and examined their levels of expression in a variety of cell lines established from human lung …

Nuclear Factor Of Activated T-Cells 5 Increases Intestinal Goblet Cell Differentiation Through An Mtor/Notch Signaling Pathway, Yuning Zhou, Qingding Wang, Heidi L. Weiss, B. Mark Evers

Markey Cancer Center Faculty Publications

The intestinal mucosa undergoes a continual process of proliferation, differentiation, and apoptosis that is regulated by multiple signaling pathways. Previously, we have shown that the nuclear factor of activated T-cells 5 (NFAT5) is involved in the regulation of intestinal enterocyte differentiation. Here we show that treatment with sodium chloride (NaCl), which activates NFAT5 signaling, increased mTORC1 repressor regulated in development and DNA damage response 1 (REDD1) protein expression and inhibited mTOR signaling; these alterations were attenuated by knockdown of NFAT5. Knockdown of NFAT5 activated mammalian target of rapamycin (mTOR) signaling and significantly inhibited REDD1 mRNA expression and protein expression. Consistently, …

Wound Healing: Biologics, Skin Substitutes, Biomembranes And Scaffolds, Krishna S. Vyas, Henry C. Vasconez

Surgery Faculty Publications

This review will explore the latest advancements spanning several facets of wound healing, including biologics, skin substitutes, biomembranes and scaffolds.

Piecing The Puzzle Together: A Revisit To Transcript Reconstruction Problem In Rna-Seq, Yan Huang, Yin Hu, Jinze Liu

Computer Science Faculty Publications

The advancement of RNA sequencing (RNA-seq) has provided an unprecedented opportunity to assess both the diversity and quantity of transcript isoforms in an mRNA transcriptome. In this paper, we revisit the computational problem of transcript reconstruction and quantification. Unlike existing methods which focus on how to explain the exons and splice variants detected by the reads with a set of isoforms, we aim at reconstructing transcripts by piecing the reads into individual effective transcript copies. Simultaneously, the quantity of each isoform is explicitly measured by the number of assembled effective copies, instead of estimated solely based on the collective read …

Calcineurin And Glial Signaling: Neuroinflammation And Beyond, Jennifer L. Furman, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

Similar to peripheral immune/inflammatory cells, neuroglial cells appear to rely on calcineurin (CN) signaling pathways to regulate cytokine production and cellular activation. Several studies suggest that harmful immune/inflammatory responses may be the most impactful consequence of aberrant CN activity in glial cells. However, newly identified roles for CN in glutamate uptake, gap junction regulation, Ca²⁺ dyshomeostasis, and amyloid production suggest that CN's influence in glia may extend well beyond neuroinflammation. The following review will discuss the various actions of CN in glial cells, with particular emphasis on astrocytes, and consider the implications for neurologic dysfunction arising with aging, injury, …

Ergovaline Stability In Tall Fescue Based On Sample Handling And Storage Methods, Krista La Moen Lea, Lori Smith, Cynthia Gaskill, Robert Coleman, S. Ray Smith

Plant and Soil Sciences Faculty Publications

Ergovaline is an ergot alkaloid produced by the endophyte Neotyphodium coenophialum (Morgan-Jones and Gams) found in tall fescue [Schedonorus arundinacea (Schreb.) Dumort.] and blamed for a multitude of livestock disorders. Ergovaline is known to be unstable and affected by many variables. The objective of this study was to determine the effect of sample handling and storage on the stability of ergovaline in tall fescue samples. Fresh tall fescue was collected from a horse farm in central Kentucky at three harvest dates and transported on ice to the University of Kentucky Veterinary Diagnostic Laboratory. Plant material was frozen in liquid …

Enhancing Immunomodulation On Innate Immunity By Shape Transition Among Rna Triangle, Square And Pentagon Nanovehicles, Emil F. Khisamutdinov, Hui Li, Daniel L. Jasinski, Jiao Chen, Jian Fu, Peixuan Guo

Center for Research on Environmental Disease Faculty Publications

Modulation of immune response is important in cancer immunotherapy, vaccine adjuvant development and inflammatory or immune disease therapy. Here we report the development of new immunomodulators via control of shape transition among RNA triangle, square and pentagon. Changing one RNA strand in polygons automatically induced the stretching of the interior angle from 60° to 90° or 108°, resulting in self-assembly of elegant RNA triangles, squares and pentagons. When immunological adjuvants were incorporated, their immunomodulation effect for cytokine TNF-α and IL-6 induction was greatly enhanced in vitro and in animals up to 100-fold, while RNA polygon controls induced unnoticeable effect. The …

Polypeptides, Nucleic Acid Molecules, And Methods For Synthesis Of Triterpenes, Joe Chappell, Thomas D. Niehaus, Shigeru Okada, Timothy P. Devarenne, David Watt

Plant and Soil Sciences Faculty Patents

This application relates to the polypeptides, nucleic acid molecules, vectors, transfected cells, and methods for synthesis of triterpenes, including botryococcene.

Repair Of O6-Methylguanine Adducts In Human Telomeric G-Quadruplex Dna By O6-Alkylguanine-Dna Alkyltransferase, Lance M. Hellman, Tyler J. Spear, Colton J. Koontz, Manana Melikishvili, Michael G. Fried

Molecular and Cellular Biochemistry Faculty Publications

O⁶-alkylguanine-DNA alkyltransferase (AGT) is a single-cycle DNA repair enzyme that removes pro-mutagenic O⁶-alkylguanine adducts from DNA. Its functions with short single-stranded and duplex substrates have been characterized, but its ability to act on other DNA structures remains poorly understood. Here, we examine the functions of this enzyme on O⁶-methylguanine (6mG) adducts in the four-stranded structure of the human telomeric G-quadruplex. On a folded 22-nt G-quadruplex substrate, binding saturated at 2 AGT:DNA, significantly less than the ~ 5 AGT:DNA found with linear single-stranded DNAs of similar length, and less than the value found with the …

Cytokine Gene Expression Profiles During Initiation, Progression And Resolution Of Periodontitis, Jeffrey L. Ebersole, Sreenatha S. Kirakodu, Michael John Novak, Arnold J. Stromberg, Shu Shen, Luis Orraca, Janis Gonzalez-Martinez, Armando Burgos, Octavio A. Gonzalez

Center for Oral Health Research Faculty Publications

AIM: Variations in the expression of cytokines during the progression of periodontitis remain ill-defined. We evaluated the expression of 19 cytokine genes related to T-cell phenotype/function during initiation, progression and resolution of periodontitis, and related these to the expression of soft and bone tissue destruction genes (TDGs).

MATERIALS AND METHODS: A ligature-induced periodontitis model was used in rhesus monkeys (M. mulatta) (n = 18). Gingival tissues were taken at baseline pre-ligation, 2 weeks and 1 month (Initiation) and 3 months (progression) post ligation. Ligatures were removed and samples taken 2 months later (resolution). Total RNA was isolated and the Rhesus …

Effect Of Soil Sampling Density And Landscape Features On Soil Test Phosphorus, Donald J. Stamper, Carmen T. Agouridis, Dwayne R. Edwards, Mark A. Purschwitz

Biosystems and Agricultural Engineering Faculty Publications

Organic and/or inorganic fertilizers are used to promote crop growth yet the rate of fertilizer application is often based on the nitrogen needs of the crop and not the phosphorus needs, especially when utilizing animal manures with low N-to-P ratios as compared to plant N:P uptake. Because of this, soil phosphorus levels in many areas of the world are in excess of crop needs. Excessive levels of phosphorus in water bodies such as streams and lakes can result in a condition known as eutrophication. With eutrophication, nutrients promote algal growth which in turn decreases dissolved oxygen levels in receiving water …

Using A Train-The-Trainer Model And Active Learning To Reach Biology Freshmen, Valerie E. Perry, Beth Reeder, Melinda Borie

Library Presentations

Using the train-the-trainer model as our foundation, we created a new information literacy program in an introductory lab course. We will describe the program’s development, implementation, and evolution since first implemented in Spring Semester 2013.We also will share the advantages of using the train-the-trainer model in an information literacy program, particularly regarding its potential to reduce librarians’ time commitment and help librarians build lasting relationships with teaching faculty and graduate students.

Lights And Larvae: Using Optogenetics To Teach Recombinant Dna And Neurobiology, John Titlow, Heidi Anderson, Robin L. Cooper

Biology Faculty Publications

Switching genes between organisms and controlling an animal’s brain using lasers may seem like science fiction, but with advancements in a technique called optogenetics, such experiments are now common in neuroscience research. Optogenetics combines recombinant DNA technology with a controlled light source to help researchers address biomedical questions in the life sciences. The technique has gained the most traction in neurobiology—the biology of the nervous system—where specific wavelengths of light are used to control or measure the activity of neurons in transgenic organisms (i.e., those with artificially inserted genes).

These optical recording and stimulation techniques are used in nervous system …

Urbanization And Stream Salamanders: A Review, Conservation Options, And Research Needs, Kyle Barrett, Steven J. Price

Forestry and Natural Resources Faculty Publications

Urban areas are increasing in size and human population density. The implications of widespread urbanization are apparent for a wide variety of stream organisms, but the responses of stream-dwelling salamanders to urbanization have been understudied historically. Studies on this assemblage have increased sufficiently over the last decade to warrant a review and synthesis of current knowledge. Our survey of the literature indicates a research bias toward species within the Piedmont ecoregion of the USA and a strong emphasis on changes in species richness, relative abundance, and occupancy along an urbanization gradient. Very few investigators have examined vital rates for specific …

Factors Limiting The Spread Of The Protective Symbiont Hamiltonella Defensa In Aphis Craccivora Aphids, Hannah R. Dykstra, Stephanie R. Weldon, Adam J. Martinez, Jennifer A. White, Keith R. Hopper, George E. Heimpel, Mark K. Asplen, Kerry M. Oliver

Entomology Faculty Publications

Many insects are associated with heritable symbionts that mediate ecological interactions, including host protection against natural enemies. The cowpea aphid, Aphis craccivora, is a polyphagous pest that harbors Hamiltonella defensa, which defends against parasitic wasps. Despite this protective benefit, this symbiont occurs only at intermediate frequencies in field populations. To identify factors constraining H. defensa invasion in Ap. craccivora, we estimated symbiont transmission rates, performed fitness assays, and measured infection dynamics in population cages to evaluate effects of infection. Similar to results with the pea aphid, Acyrthosiphon pisum, we found no consistent costs to infection using …

Comparison Of Isokinetic Hip Abduction And Adduction Peak Torques And Ratio Between Sexes, Dai Sugimoto, Carl G. Mattacola, David R. Mullineaux, Thomas Gerard Palmer, Timothy E. Hewett

Physical Therapy Faculty Publications

OBJECTIVE: To evaluate hip abductor and adductor peak torque outputs and compare their ratios between sexes.

DESIGN: A cross-sectional laboratory-controlled study.

SETTING: Participants visited a laboratory and performed an isokinetic hip abductor and adductor test. All participants performed 2 sets of 5 repetitions of concentric hip abduction and adduction in a standing position at 60 degrees per second. Gravity was determined as a function of joint angle relative to the horizontal plane and was corrected by normalizing the weight of the limb on an individual basis.

PARTICIPANTS: A total of 36 collegiate athletes.

INDEPENDENT VARIABLES: Sex (20 females and 16 …

A Novel Partitivirus That Confers Hypovirulence On Plant Pathogenic Fungi, Xueqiong Xiao, Jiasen Cheng, Jinghua Tang, Yanping Fu, Daohong Jiang, Timothy S. Baker, Said A. Ghabrial, Jiatao Xie

Plant Pathology Faculty Publications

Members of the family Partitiviridae have bisegmented double-stranded RNA (dsRNA) genomes and are not generally known to cause obvious symptoms in their natural hosts. An unusual partitivirus, Sclerotinia sclerotiorum partitivirus 1 (SsPV1/WF-1), conferred hypovirulence on its natural plant-pathogenic fungal host, Sclerotinia sclerotiorum strain WF-1. Cellular organelles, including mitochondria, were severely damaged. Hypovirulence and associated traits of strain WF-1 and SsPV1/WF-1 were readily cotransmitted horizontally via hyphal contact to different vegetative compatibility groups of S. sclerotiorum and interspecifically to Sclerotinia nivalis and Sclerotinia minor. S. sclerotiorum strain 1980 transfected with purified SsPV1/WF-1 virions also exhibited hypovirulence and associated traits similar …

Survival Advantage Associated With Decrease In Stage At Detection From Stage Iiic To Stage Iiia Epithelial Ovarian Cancer, John Hoff, Lauren Baldwin, Jason Lefringhouse, Edward J. Pavlik, Rachel Miller, Christopher Desimone, Frederick Ueland, Thomas Tucker, Richard Kryscio, John R. Van Nagell Jr.

Markey Cancer Center Faculty Publications

Objective. The aim of this study was to document the survival advantage of lowering stage at detection from Stage IIIC to Stage IIIA epithelial ovarian cancer. Methods. Treatment outcomes and survival were evaluated in patients with Stage IIIA and Stage IIIC epithelial ovarian cancer treated from 2000 to 2009 at the University of Kentucky Markey Cancer Center (UKMCC) and SEER institutions. Results. Cytoreduction to no visible disease (P < 0.0001) and complete response to platinum-based chemotherapy (P < 0.025) occurred more frequently in Stage IIIA than in Stage IIIC cases. Time to progression was shorter in patients with Stage IIIC ovarian cancer (17 ± 1 months) than in those with Stage II1A disease (36 ± 8 months). Five-year overall survival (OS) improved from 41% in Stage IIIC patients to 60% in Stage IIIA patients treated at UKMCC and from 37% to 56% in patients treated at SEER institutions for a survival advantage of 19% in both data sets. 53% of Stage IIIA and 14% of Stage IIIC patients had NED at last followup. Conclusions. Decreasing stage at detection from Stage IIIC to stage IIIA epithelial ovarian cancer is associated with a 5-year survival advantage of nearly 20% in patients treated by surgical tumor …

Fructose-2,6-Bisphosphate Synthesis By 6-Phosphofructo-2-Kinase/Fructose-2,6-Bisphosphatase 4 (Pfkfb4) Is Required For The Glycolytic Response To Hypoxia And Tumor Growth, Jason Chesney, Jennifer Clark, Alden C. Klarer, Yoannis Imbert-Fernandez, Andrew N. Lane, Sucheta Telang

Markey Cancer Center Faculty Publications

Fructose-2,6-bisphosphate (F2,6BP) is a shunt product of glycolysis that allosterically activates 6-phosphofructo-1-kinase (PFK-1) resulting in increased glucose uptake and glycolytic flux to lactate. The F2,6BP concentration is dictated by four bifunctional 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases (PFKFB1-4) with distinct kinase:phosphatase activities. PFKFB4 is over-expressed in human cancers, induced by hypoxia and required for survival and growth of several cancer cell lines. Although PFKFB4 appears to be a rational target for anti-neoplastic drug development, it is not clear whether its kinase or phosphatase activity is required for cancer cell survival. In this study, we demonstrate that recombinant human PFKFB4 kinase activity is 4.3-fold greater than …

An Intronic Picalm Polymorphism, Rs588076, Is Associated With Allelic Expression Of A Picalm Isoform, Ishita Parikh, Christopher Medway, Steven Younkin, David Fardo, Steven Estus

Physiology Faculty Publications

BACKGROUND: Although genome wide studies have associated single nucleotide polymorphisms (SNP)s near PICALM with Alzheimer's disease (AD), the mechanism underlying this association is unclear. PICALM is involved in clathrin-mediated endocytosis and modulates Aß clearance in vitro. Comparing allelic expression provides the means to detect cis-acting regulatory polymorphisms. Thus, we evaluated whether PICALM showed allele expression imbalance (AEI) and whether this imbalance was associated with the AD-associated polymorphism, rs3851179.

RESULTS: We measured PICALM allelic expression in 42 human brain samples by using next-generation sequencing. Overall, PICALM demonstrated equal allelic expression with no detectable influence by rs3851179. A single sample demonstrated …

Paternal Incarceration And Children's Food Insecurity: A Consideration Of Variation And Mechanisms, Kristen Turney

University of Kentucky Center for Poverty Research Discussion Paper Series

Despite growing attention to the unintended consequences of paternal incarceration for children’s wellbeing across the life course, little is known about whether and how paternal incarceration is related to food insecurity among children, an especially acute and severe form of deprivation. In this article, I use data from the Fragile Families and Child Wellbeing Study, a cohort of children born to mostly unmarried mothers, to examine the relationship between paternal incarceration and three indicators of food insecurity among young children: current food insecurity (at age five), onset of food insecurity (between ages three and five), and exit from food insecurity …

Childhood Stress: A Qualitative Analysis Of The Intergenerational Circumstances Of Child Hunger, Mariana Chilton, Molly Knowles

University of Kentucky Center for Poverty Research Discussion Paper Series

Adverse Childhood Experiences (ACEs), including abuse, neglect, and household instability, affect lifelong health and economic potential. While relationships between household food insecurity and caregiver’s childhood exposure to abuse and neglect are underexplored, preliminary evidence indicates that caregivers reporting very low food security report traumatic events in their childhoods that lead to poor physical and mental health. Building on this evidence, this study investigates how adverse childhood experiences are associated with the intergenerational transmission of household food insecurity.

Applying Accelerator Mass Spectrometry For Low-Level Detection Of Complex Engineered Nanoparticles In Biological Media, Binghui Wang, George S. Jackson, Robert A. Yokel, Eric A. Grulke

Pharmaceutical Sciences Faculty Publications

Complex engineered nanoparticles (CENPs), which have different core and surface components, are being developed for medicinal, pharmaceutical and industrial applications. One of the key challenges for environmental health and safety assessments of CENPs is to identify and quantity their transformations in biological environments. This study reports the effects of in vivo exposure of citrate-coated nanoalumina with different rare isotope labels on each component. This CENP was dosed to the rat and accelerator mass spectrometry (AMS) was used to quantify ²⁶Al, ¹⁴C, and their ratio in the dosing material and tissue samples. For CENPs detected in the liver, the …

Racial Disparities In Access To Community Water Supply Service In Wake County, North Carolina, Jacqueline Macdonald Gibson, Nicholas Defelice, Daniel Sebastian, Hannah Leker

Frontiers in Public Health Services and Systems Research

Anecdotal evidence suggests that historically African American communities on the fringes of cities and towns in North Carolina have been systematically denied access to municipal drinking water service. This paper presents the first statistical analysis of the role of race in determining water access in these fringe areas, known as extraterritorial jurisdictions. Using publicly available property tax data, we quantified the percentage of residences with municipal water service in each census block in Wake County (the second-largest by population in North Carolina). Using the resulting water service maps plus 2010 U.S. Census data, we employed a logistic regression to assess …

Lipid Extraction From Scenedesmus Sp. Microalgae For Biodiesel Production Using Hot Compressed Hexane, Hee-Yong Shin, Jae-Hun Ryu, Seong-Youl Bae, Czarena L. Crofcheck, Mark Crocker

Center for Applied Energy Research Faculty and Staff Publications

Lipid extraction from Scenedesmus sp. microalgae using hot compressed hexane (HCH) was investigated. Extraction performance was evaluated near the critical point of hexane and was compared with that of hexane extraction performed at room temperature and pressure, and the Bligh and Dyer extraction method. Experimental data showed that HCH significantly improves the lipid yield and rate of lipid extraction compared to the use of hexane at ambient conditions. High yields of biodiesel-convertible lipid fractions were rapidly achieved at the critical point of hexane, at a level comparable to that of the Bligh and Dyer method.

Generation And Behavior Characterization Of Camkiiβ Knockout Mice, Adam D. Bachstetter, Scott J. Webster, Tao Tu, Danielle S. Goulding, Jacques Haiech, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

The calcium/calmodulin-dependent protein kinase II (CaMKII) is abundant in the brain, where it makes important contributions to synaptic organization and homeostasis, including playing an essential role in synaptic plasticity and memory. Four genes encode isoforms of CaMKII (α, β, δ, γ), with CaMKIIα and CaMKIIβ highly expressed in the brain. Decades of molecular and cellular research, as well as the use of a large number of CaMKIIα mutant mouse lines, have provided insight into the pivotal roles of CaMKIIα in brain plasticity and cognition. However, less is known about the CaMKIIβ isoform. We report the development and extensive behavioral and …

Mixtures Of Self-Modelling Regressions, Rhonda D. Szczesniak, Kert Viele, Robin L. Cooper

Statistics Faculty Publications

A shape invariant model for functions f₁,...,f_n specifies that each individual function f_i can be related to a common shape function g through the relation f_i(x) = a_ig(c_ix + d_i) + b_i. We consider a flexible mixture model that allows multiple shape functions g₁,...,g_K, where each f_i is a shape invariant transformation of one of those g_K. We derive an MCMC algorithm for fitting the model using Bayesian Adaptive Regression Splines (BARS), propose …

Loss Of 4e-Bp1 Function Induces Emt And Promotes Cancer Cell Migration And Invasion Via Cap-Dependent Translational Activation Of Snail, Weijia Cai, Qing Ye, Qing-Bai She

Markey Cancer Center Faculty Publications

The cap-dependent translation is frequently deregulated in a variety of cancers associated with tumor progression. However, the molecular basis of the translation activation for metastatic progression of cancer remains largely elusive. Here, we demonstrate that activation of cap-dependent translation by silencing the translational repressor 4E-BP1 causes cancer epithelial cells to undergo epithelial-mesenchymal transition (EMT), which is associated with selective upregulation of the EMT inducer Snail followed by repression of E-cadherin expression and promotion of cell migratory and invasive capabilities as well as metastasis. Conversely, inhibition of cap-dependent translation by a dominant active mutant 4E-BP1 effectively downregulates Snail expression and suppresses …

Molecular Xenomonitoring Using Mosquitoes To Map Lymphatic Filariasis After Mass Drug Administration In American Samoa, Mark A. Schmaedick, Amanda L. Koppel, Nils Pilotte, Melissa Torres, Steven A. Williams, Stephen L. Dobson, Patrick J. Lammie, Kimberly Y. Won

Entomology Faculty Publications

BACKGROUND: Mass drug administration (MDA) programs have dramatically reduced lymphatic filariasis (LF) incidence in many areas around the globe, including American Samoa. As infection rates decline and MDA programs end, efficient and sensitive methods for detecting infections are needed to monitor for recrudescence. Molecular methods, collectively termed 'molecular xenomonitoring,' can identify parasite DNA or RNA in human blood-feeding mosquitoes. We tested mosquitoes trapped throughout the inhabited islands of American Samoa to identify areas of possible continuing LF transmission after completion of MDA.

METHODOLOGY/PRINCIPLE FINDINGS: Mosquitoes were collected using BG Sentinel traps from most of the villages on American Samoa's largest …