Digital Commons Network^™

A Phase Ii Study Of Pulse Dose Imatinib Mesylate And Weekly Paclitaxel In Patients Aged 70 And Over With Advanced Non-Small Cell Lung Cancer, Julie E. Bauman, Keith D. Eaton, Sarah G. Wallace, Laurie L. Carr, Sang-Joon Lee, Dennie V. Jones, Hugo Arias-Pulido, Lisa A. Cerilli, Renato G. Martins

Internal Medicine Faculty Publications

BACKGROUND: In non-small cell lung cancer (NSCLC), interstitial hypertension is a barrier to chemotherapy delivery, and is mediated by platelet derived growth factor receptor (PDGFR). Antagonizing PDGFR with imatinib may improve intra-tumoral delivery of paclitaxel, increasing response rate (RR).

METHODS: This single-stage, open-label phase II study evaluated pulse dose imatinib and weekly paclitaxel in elderly patients with advanced NSCLC. Eligible patients were aged ≥ 70 with untreated, stage IIIB-IV NSCLC and ECOG performance status 0-2. Primary endpoint was RR. Secondary endpoints included median progression free and overall survival (PFS, OS) and correlatives of PDGFR pathway activation. Baseline Charlson Comorbidity Index …

Family Structure, Work Patterns And Time Allocations: Potential Mechanisms Of Food Insecurity Among Children, Kelly Balistreri

University of Kentucky Center for Poverty Research Discussion Paper Series

Over 469 thousand households in the U.S. experienced very low food security among children, a severe condition characterized by reductions in food intake due to an inability to afford enough food. But food insecurity is not simply about economic resources. There exists a paradox in which some poor households with children are food secure while some non-poor households with children are food insecure. This study moves beyond a singular focus on income and considers how the family context may protect or generate risk of food insecurity for children. The goals of the proposed project were to: 1) to provide a …

Envisioning An Oral Healthcare Workforce For The Future, David A. Nash

Oral Health Science Faculty Publications

Health is critical to human well-being. Oral health is an integral component of health. One is not healthy without oral health. As health is essential to human flourishing, it is important that an oral healthcare delivery system and workforce be developed and deployed which can help ensure all citizens have the potential to access oral health care. As such access does not generally exist today, it is imperative to advance the realization of this goal and to develop a vision of an oral healthcare workforce to functionally support access. Public funding of basic oral health care is an important element …

Grave Robbing In Lexington And Elsewhere, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

No abstract provided.

Rat Brain Pro-Oxidant Effects Of Peripherally Administered 5 Nm Ceria 30 Days After Exposure, Sarita S. Hardas, Rukhsana Sultana, Govind Warrier, Mo Dan, Rebecca L. Florence, Peng Wu, Eric A. Grulke, Michael T. Tseng, Jason M. Unrine, Uschi M. Graham, Robert A. Yokel, D. Allan Butterfield

Chemistry Faculty Publications

The objective of this study was to determine the residual pro-or anti-oxidant effects in rat brain 30 days after systemic administration of a 5 nm citrate-stabilized ceria dispersion. A ∼4% aqueous ceria dispersion was iv-infused (0 or 85 mg/kg) into rats which were terminated 30 days later. Ceria concentration, localization, and chemical speciation in the brain was assessed by inductively coupled plasma mass spectrometry (ICP-MS), light and electron microscopy (EM), and electron energy loss spectroscopy (EELS), respectively. Pro- or anti-oxidant effects were evaluated by measuring levels of protein carbonyls (PC), 3-nitrotyrosine (3NT), and protein-bound-4-hydroxy-2-trans-nonenal (HNE) in the hippocampus, cortex, and …

Doxycycline Does Not Influence Established Abdominal Aortic Aneurysms In Angiotensin Ii-Infused Mice, Xiaojie Xie, Hong Lu, Jessica J. Moorleghen, Deborah A. Howatt, Debra L. Rateri, Lisa A. Cassis, Alan Daugherty

Saha Cardiovascular Research Center Faculty Publications

Background: There is no proven medical approach to attenuating expansion and rupture of abdominal aortic aneurysms (AAAs). One approach that is currently being investigated is the use of doxycycline. Despite being primarily used as an antimicrobial drug, doxycycline has been proposed to function in reducing AAA expansion. Doxycycline is effective in reducing the formation in the most commonly used mouse models of AAAs when administered prior to the initiation of the disease. The purpose of the current study was to determine the effects of doxycycline on established AAAs when it was administered at a dose that produces therapeutic serum …

Latexin Is Down-Regulated In Hematopoietic Malignancies And Restoration Of Expression Inhibits Lymphoma Growth, Yi Liu, Dianna Howard, Kyle Rector, Carol Swiderski, Jason Brandon, Lawrence Schook, Jayesh Mehta, J. Scott Bryson, Subbarao Bondada, Ying Liang

Internal Medicine Faculty Publications

Latexin is a negative regulator of hematopoietic stem cell number in mice. Its dysregulated expression in other tumors led us to hypothesize that latexin may have tumor suppressor properties in hematological malignancies. We found that latexin was down-regulated in a variety of leukemia and lymphoma cell lines as well as in CD34+ cells from the blood and marrow of patients with these malignancies. 5-aza-2'-deoxycytodine treatment and bisulfite sequencing revealed hypermethylation of latexin promoter in tumor cells. Retrovirus-mediated latexin overexpression in A20 mouse lymphoma cells inhibited their in vitro growth by 16 fold and in vivo tumor volume by 2 fold. …

Seed Dimorphism, Nutrients And Salinity Differentially Affect Seed Traits Of The Desert Halophyte Suaeda Aralocaspica Via Multiple Maternal Effects, Lei Wang, Jerry M. Baskin, Carol C. Baskin, J. Hans C. Cornelissen, Ming Dong, Zhenying Huang

Biology Faculty Publications

BACKGROUND: Maternal effects may influence a range of seed traits simultaneously and are likely to be context-dependent. Disentangling the interactions of plant phenotype and growth environment on various seed traits is important for understanding regeneration and establishment of species in natural environments. Here, we used the seed-dimorphic plant Suaeda aralocaspica to test the hypothesis that seed traits are regulated by multiple maternal effects.

RESULTS: Plants grown from brown seeds had a higher brown:black seed ratio than plants from black seeds, and germination percentage of brown seeds was higher than that of black seeds under all conditions tested. However, the coefficient …

Molecular Characterization Of The Viab Locus Encoding The Biosynthetic Machinery For Vi Capsule Formation In Salmonella Typhi, Michael Wetter, David Goulding, Derek Pickard, Michael Kowarik, Charles J. Waechter, Gordon Dougan, Michael Wacker

Molecular and Cellular Biochemistry Faculty Publications

The Vi capsular polysaccharide (CPS) of Salmonella enterica serovar Typhi, the cause of human typhoid, is important for infectivity and virulence. The Vi biosynthetic machinery is encoded within the viaB locus composed of 10 genes involved in regulation of expression (tviA), polymer synthesis (tviB-tviE), and cell surface localization of the CPS (vexA-vexE). We cloned the viaB locus from S. Typhi and transposon insertion mutants of individual viaB genes were characterized in Escherichia coli DH5α. Phenotype analysis of viaB mutants revealed that tviB, tviC, tviD and tviE are involved in Vi polymer synthesis. Furthermore, expression of tviB-tviE in E. coli DH5α …

Serotonin And Synaptic Transmission At Invertebrate Neuromuscular Junctions, Wen-Hui Wu, Robin L. Cooper

Biology Faculty Publications

The serotonergic system in vertebrates and invertebrates has been a focus for over 50 years and will likely continue in the future. Recently, genomic analysis and discovery of alternative splicing and differential expression in tissues have increased the knowledge of serotonin (5-HT) receptor types. Comparative studies can provide useful insights to the wide variety of mechanistic actions of 5-HT responsible for behaviors regulated or modified by 5-HT. To determine cellular responses and influences on neural systems as well as the efferent control of behaviors by the motor units, preparations amenable to detailed studies of synapses are beneficial as working models. …

Perlecan Domain V Induces Vegf Secretion In Brain Endothelial Cells Through Integrin Α5Β1 And Erk-Dependent Signaling Pathways, Douglas N. Clarke, Abraham Al Ahmad, Boyeon Lee, Christi Parham, Lisa Auckland, Andrezj Fertala, Michael Kahle, Courtney S. Shaw, Jill Roberts, Gregory J. Bix

Sanders-Brown Center on Aging Faculty Publications

Perlecan Domain V (DV) promotes brain angiogenesis by inducing VEGF release from brain endothelial cells (BECs) following stroke. In this study, we define the specific mechanism of DV interaction with the α(5)β(1) integrin, identify the downstream signal transduction pathway, and further investigate the functional significance of resultant VEGF release. Interestingly, we found that the LG3 portion of DV, which has been suggested to possess most of DV's angio-modulatory activity outside of the brain, binds poorly to α(5)β(1) and induces less BEC proliferation compared to full length DV. Additionally, we implicate DV's DGR sequence as an important element for the interaction …

Cytochrome P450s And Uses Thereof, Joe Chappell, Lyle F. Ralston

Plant and Soil Sciences Faculty Patents

The invention features isolated cytochrome P450 polypeptides and nucleic acid molecules, as well as expression vectors and transgenic plants containing these molecules. In addition, the invention features uses of such molecules in methods of increasing the level of resistance against a disease caused by a plant pathogen in a transgenic plant, in methods for producing altered compounds, for example, hydroxylated compounds, and in methods of producing isoprenoid compounds.

Widespread And Persistent Invasions Of Terrestrial Habitats Coincident With Larval Feeding Behavior Transitions During Snail-Killing Fly Evolution (Diptera: Sciomyzidae), Eric G. Chapman, Andrey A. Przhiboro, James D. Harwood, Benjamin A. Foote, Walter R. Hoeh

Entomology Faculty Publications

BACKGROUND: Transitions in habitats and feeding behaviors were fundamental to the diversification of life on Earth. There is ongoing debate regarding the typical directionality of transitions between aquatic and terrestrial habitats and the mechanisms responsible for the preponderance of terrestrial to aquatic transitions. Snail-killing flies (Diptera: Sciomyzidae) represent an excellent model system to study such transitions because their larvae display a range of feeding behaviors, being predators, parasitoids or saprophages of a variety of mollusks in freshwater, shoreline and dry terrestrial habitats. The remarkable genus Tetanocera (Tetanocerini) occupies five larval feeding groups and all of the habitat types mentioned above. …

Kentucky Water Resources Research Institute Center Of Excellence For Watershed Management Watershed Summit Summary Report, Kentucky Water Resources Research Institute, University Of Kentucky

KWRRI Research Reports

No abstract provided.

Characterizing Physical Properties Of Gas-Phase Biofilter Media, Guilherme Del Nero Maia, G. Tatiana Sales, George B. Day V, Richard S. Gates, Joseph L. Taraba

Biosystems and Agricultural Engineering Faculty Publications

Gas-phase biofiltration is an effective technology for reduction of odors and trace-gas contaminants. Significant contributions to the technical literature regarding the characterization of biofilter media have been generated in the past two decades. Nevertheless, the information produced has not been systematically organized. The objective of this study is to demonstrate and document methods for physical characterization of gas-phase compost biofilters (GPCB). The inclusion of moisture content, compaction, and particle size effects in the determination of media bulk density and porosity, field capacity, drying rate analysis, water sorption isotherms, and resistance to airflow is demonstrated. Results indicated that: (1) higher moisture …

Borrelia Burgdorferi Cp32 Bpab Modulates Expression Of The Prophage Nucp Nuclease And Ssbp Single-Stranded Dna-Binding Protein, Alicia M. Chenail, Brandon L. Jutras, Claire A. Adams, Logan H. Burns, Amy Bowman, Ashutosh Verma, Brian Stevenson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The Borrelia burgdorferi BpaB proteins of the spirochete's ubiquitous cp32 prophages are DNA-binding proteins, required both for maintenance of the bacteriophage episomes and for transcriptional regulation of the cp32 erp operons. Through use of DNase I footprinting, we demonstrate that BpaB binds the erp operator initially at the sequence 5′-TTATA-3′. Electrophoretic mobility shift assays indicated that BpaB also binds with high affinity to sites located in the 5′ noncoding regions of two additional cp32 genes. Characterization of the proteins encoded by those genes indicated that they are a single-stranded DNA-binding protein and a nuclease, which we named SsbP and NucP, …

Sarcopenia, Obesity, And Natural Killer Cell Immune Senescence In Aging: Altered Cytokine Levels As A Common Mechanism, Charles T. Lutz, Lebris S. Quinn

Pathology and Laboratory Medicine Faculty Publications

Human aging is characterized by both physical and physiological frailty. A key feature of frailty, sarcopenia is the age-associated decline in skeletal muscle mass, strength, and endurance that characterize even the healthy elderly. Increases in adiposity, particularly in visceral adipose tissue, are almost universal in aging individuals and can contribute to sarcopenia and insulin resistance by increasing levels of inflammatory cytokines known collectively as adipokines. Aging also is associated with declines in adaptive and innate immunity, known as immune senescence, which are risk factors for cancer and all-cause mortality. The cytokine interleukin-15 (IL-15) is highly expressed in skeletal muscle tissue …

Transcriptional Repression Of Sodium-Iodide Symporter In Thyroid Carcinoma, Kenneth B. Ain, Wei Li

Internal Medicine Faculty Patents

The present disclosure relates to a sodium iodide symporter (NIS)-repressor binding site (NRBS) consisting of a DNA molecule spanning from −645 to −605 nucleotides (SEQ ID NO:4) or from −648 to −620 nucleotides (SEQ ID NO:5) upstream from the translation start site of human NIS gene. The disclosure further relates to a method of restoring iodide transport to a human thyroid carcinoma cell, including: the steps of: i) contacting the cell expressing and forming a NIS repressor protein complex capable of binding to the NRBS of the disclosure with a modulator of said complex, and ii) administering to the cell …

Role Of Sequence And Structure Of The Hendra Fusion Protein Fusion Peptide In Membrane Fusion, Everett Clinton Smith, Sonia M. Gregory, Lukas K. Tamm, Trevor P. Creamer, Rebecca Ellis Dutch

Molecular and Cellular Biochemistry Faculty Publications

Viral fusion proteins are intriguing molecular machines that undergo drastic conformational changes to facilitate virus-cell membrane fusion. During fusion a hydrophobic region of the protein, termed the fusion peptide (FP), is inserted into the target host cell membrane, with subsequent conformational changes culminating in membrane merger. Class I fusion proteins contain FPs between 20 and 30 amino acids in length that are highly conserved within viral families but not between. To examine the sequence dependence of the Hendra virus (HeV) fusion (F) protein FP, the first eight amino acids were mutated first as double, then single, alanine mutants. Mutation of …

Sex Determination In Beetles: Production Of All Male Progeny By Parental Rnai Knockdown Of Transformer, Jayendra Nath Shukla, Subba Reddy Palli

Entomology Faculty Publications

Sex in insects is determined by a cascade of regulators ultimately controlling sex-specific splicing of a transcription factor, Doublesex (Dsx). We recently identified homolog of dsx in the red flour beetle, Tribolium castaneum (Tcdsx). Here, we report on the identification and characterization of a regulator of Tcdsx splicing in T. castaneum. Two male-specific and one female-specific isoforms of T. castaneum transformer (Tctra) were identified. RNA interference-aided knockdown of Tctra in pupa or adults caused a change in sex from females to males by diverting the splicing of Tcdsx pre-mRNA to male-specific isoform. All the pupa and adults developed from Tctra …

A Support Vector Machine Based Test For Incongruence Between Sets Of Trees In Tree Space, David C. Haws, Peter Huggins, Eric M. O'Neill, David W. Weisrock, Ruriko Yoshida

Statistics Faculty Publications

BACKGROUND: The increased use of multi-locus data sets for phylogenetic reconstruction has increased the need to determine whether a set of gene trees significantly deviate from the phylogenetic patterns of other genes. Such unusual gene trees may have been influenced by other evolutionary processes such as selection, gene duplication, or horizontal gene transfer.

RESULTS: Motivated by this problem we propose a nonparametric goodness-of-fit test for two empirical distributions of gene trees, and we developed the software GeneOut to estimate a p-value for the test. Our approach maps trees into a multi-dimensional vector space and then applies support vector machines (SVMs) …

Coronary Artery Remodeling In A Model Of Left Ventricular Pressure Overload Is Influenced By Platelets And Inflammatory Cells, Fanmuyi Yang, Anping Dong, Paul Mueller, Jessica Caicedo, Alyssa Moore Sutton, Juliana Odetunde, Cordelia J. Barrick, Yuri M. Klyachkin, Ahmed Abdel-Latif, Susan S. Smyth

Internal Medicine Faculty Publications

Left ventricular hypertrophy (LVH) is usually accompanied by intensive interstitial and perivascular fibrosis, which may contribute to arrhythmogenic sudden cardiac death. The mechanisms underlying the development of cardiac fibrosis are incompletely understood. To investigate the role of perivascular inflammation in coronary artery remodeling and cardiac fibrosis during hypertrophic ventricular remodeling, we used a well-established mouse model of LVH (transverse aortic constriction [TAC]). Three days after pressure overload, macrophages and T lymphocytes accumulated around and along left coronary arteries in association with luminal platelet deposition. Consistent with these histological findings, cardiac expression of IL-10 was upregulated and in the systemic circulation, …

Genomics Of Mature And Immature Olfactory Sensory Neurons, Melissa D. Nickell, Patrick Breheny, Arnold J. Stromberg, Timothy S. Mcclintock

Physiology Faculty Publications

The continuous replacement of neurons in the olfactory epithelium provides an advantageous model for investigating neuronal differentiation and maturation. By calculating the relative enrichment of every mRNA detected in samples of mature mouse olfactory sensory neurons (OSNs), immature OSNs, and the residual population of neighboring cell types, and then comparing these ratios against the known expression patterns of >300 genes, enrichment criteria that accurately predicted the OSN expression patterns of nearly all genes were determined. We identified 847 immature OSN-specific and 691 mature OSN-specific genes. The control of gene expression by chromatin modification and transcription factors, and neurite growth, protein …

An Examination Of Maternal Stress, Inflammatory Markers, And Preterm Labor In Pregnant Women, Cecilia Boateng

Kaleidoscope

No abstract provided.

Novel Role Of A Cypovirus In Polydnavirus-Parasitoid-Host Relationship, Philip Houtz

Kaleidoscope

No abstract provided.

Childhood Depression And Obesity: Role Of The Hypothalamic-Pituitary-Adrenal (Hpa) Axis Activity, Joanne Tyler

Kaleidoscope

This study examined relations between child depression and eating behavior and weight problems, including the role ofbaseline cortisol and cortisol reactivity in these relations. Data were drawn from a larger study, and included 50 children between the ages of6 and 12. Children reported on their depressive symptoms, and children and parents reported on child engagement in external eating, under-eating, over-eating, parental pressure to eat, enjoyment of food, and food and satiety responsiveness. For children exhibiting hypercortisolism, depression was associated with decreased over-eating and food responsiveness. Hypercortisolism was especially important for girls and children later in pubertal development. The reduced appetite …

Morphological And Genetic Activation Of Microglia After Diffuse Traumatic Brain Injury In The Rat, Tuoxin Caou, Amanda M. Lisembee, Kelley D. Hall, James R. Pauly, Jonathan Lifshitz

Kaleidoscope

Traumatic brain injury (TBI) survivors experience long, term post-traumatic morbidities. In diffuse brain injured rats, a chronic sensory sensitivity to whisker stimulation models agitation in brain injury survivors and provides anatomical landmarks across the whisker-barrel circuit to evaluate traumatic neuropathology. As a consequence of TBI, acute and chronic microglial activation can contribute to degenerative and reparative events underlying post-traumatic morbidity. Here, we hypothesize that delayed microglial activation is concomitant with neuroplastic change after diffuse brain injury in the rat, by examining differential microglial activation states and neuroplasticity through gene and protein expression. Adult male, Sprague-Dawley rats were subjected to a …

Hormonal Induction Of Polo-Like Kinases (Plks) And Impact Of Plk2 On Cell Cycle Progression In The Rat Ovary, Feixue Li, Misung Jo, Thomas E. Curry, Jing Liu

Obstetrics and Gynecology Faculty Publications

The highly conserved polo-like kinases (Plks) are potent regulators of multiple functions in the cell cycle before and during mitotic cell division. We investigated the expression pattern of Plk genes and their potential role(s) in the rat ovary during the periovulatory period. Plk2 and Plk3 were highly induced both in intact ovaries and granulosa cells in vivo after treatment with the luteinizing hormone (LH) agonist, human chorionic gonadotropin (hCG). In vitro, hCG stimulated the expression of Plk2 in granulosa cells, but not Plk3. This induction of Plk2 expression was mimicked by both forskolin and phorbol 12 myristate 13-acetate (PMA). Moreover, …

The Acute And Chronic Effect Of Low Temperature On Survival, Heart Rate And Neural Function In Crayfish (Procambarus Clarkii) And Prawn (Macrobrachium Rosenbergii) Species, Yoo Sun Chung, Richard M. Cooper, Justin Graff, Robin L. Cooper

Biology Faculty Publications

The effect of acute and chronic cold exposure on heart rate (HR) and neuronal function in crayfish Procambarus clarkii and prawns Macrobrachium rosenbergii was addressed. This is particularly important since prawn farms of this species are used for aquaculture in varied climates world wide. The success of P. clarkii as an invasive species throughout the world may in part be due to their ability to acclimate to cold and warm habitats. A set of experiments was devised to address the physiological abilities of these species in managing rapid changes to cold environments as well as their ability to respond to …

Ultrastable Synergistic Tetravalent Rna Nanoparticles For Targeting To Cancers, Farzin Haque, Dan Shu, Yi Shu, Luda S. Shlyakhtenko, Piotr G. Rychahou, B. Mark Evers, Peixuan Guo

Pharmaceutical Sciences Faculty Publications

One of the advantages of nanotechnology is the feasibility to construct therapeutic particles carrying multiple therapeutics with defined structure and stoichiometry. The field of RNA nanotechnology is emerging. However, controlled assembly of stable RNA nanoparticles with multiple functionalities which retain their original role is challenging due to refolding after fusion. Herein, we report the construction of thermodynamically stable X-shaped RNA nanoparticles to carry four therapeutic RNA motifs by self-assembly of reengineered small RNA fragments. We proved that each arm of the four helices in the X-motif can harbor one siRNA, ribozyme, or aptamer without affecting the folding of the central …