Life Sciences Commons^™

Modeling Measurement Error In Tumor Characterization Studies, Cyril Rakovski, Daniel J. Weisenberger, Paul Marjoram, Peter W. Laird, Kimberly D. Siegmund

Mathematics, Physics, and Computer Science Faculty Articles and Research

Background: Etiologic studies of cancer increasingly use molecular features such as gene expression, DNA methylation and sequence mutation to subclassify the cancer type. In large population-based studies, the tumor tissues available for study are archival specimens that provide variable amounts of amplifiable DNA for molecular analysis. As molecular features measured from small amounts of tumor DNA are inherently noisy, we propose a novel approach to improve statistical efficiency when comparing groups of samples. We illustrate the phenomenon using the MethyLight technology, applying our proposed analysis to compare MLH1 DNA methylation levels in males and females studied in the Colon …

The Energy Landscape Analysis Of Cancer Mutations In Protein Kinases, Anshuman Dixit, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

The growing interest in quantifying the molecular basis of protein kinase activation and allosteric regulation by cancer mutations has fueled computational studies of allosteric signaling in protein kinases. In the present study, we combined computer simulations and the energy landscape analysis of protein kinases to characterize the interplay between oncogenic mutations and locally frustrated sites as important catalysts of allostetric kinase activation. While structurally rigid kinase core constitutes a minimally frustrated hub of the catalytic domain, locally frustrated residue clusters, whose interaction networks are not energetically optimized, are prone to dynamic modulation and could enable allosteric conformational transitions. The results …

Conformation And Ion Transport Of Neuronal Uncoupling Proteins: Ucp2, Ucp4, And Ucp5, Tuan Hoang

Theses and Dissertations (Comprehensive)

Located in the inner mitochondrial membrane of brown adipose tissue, uncoupling protein -1 (UCP1) dissipates the proton electrochemical gradient, causing reduction in the rate of ATP synthesis, and generates heat by non-shivering thermogenesis. Three other UCP homologs (UCP2, UCP4 and UCP5), expressed in neurons, are suggested to have potential roles in the function and protection of the central nervous system (CNS). Up to date, structural information for UCPs still remains limited. Extensive biochemical studies on UCP2 have provided adequate evidence for its participation in proton and anion transport. So far, no functional studies in proteoliposome systems have been performed on …

The Role Of The Acidic Domain Of The Toc159 Protein Import Receptor Family In Toc Complex Assembly In Arabidopsis Thaliana, Yi Chen

Theses and Dissertations (Comprehensive)

Most chloroplast proteins are encoded in the nucleus and translated in the cytosol with an N-terminal cleavable transit peptide, which can be recognized by the translocon at the outer envelope membrane of chloroplasts (Toc complex). The core Toc complex is composed of two GTPases, Toc159 and Toc34, and the Toc75 channel. atToc159, atToc132 and atToc120 are homologues of the Toc159 family in Arabidopsis, and have been shown to assemble into structurally and functionally distinct Toc complexes. Targeting of atToc159 to the chloroplast outer membrane is mediated by its GTPase (G-) domain. However, the role of the acidic (A-) domain in …

Effects Of 3-Trifluoromethyl-4-Nitrophenol (Tfm) On Energy Stores And Gill Function In Sea Lamprey (Petromyzon Marinus) And Rainbow Trout (Oncorhynchus Mykiss), Matthew Henry

Theses and Dissertations (Comprehensive)

The primary method of controlling invasive sea lamprey (Petromyzon marinus) populations in the Great Lakes is the application of the pesticide 3-trifluoromethyl-4-nitrophenol (TFM) to larval lamprey nursery streams. Recent evidence suggests that the mode of toxic action of TFM involves the inhibition of oxidative ATP production in the mitochondria. As a result, there is increased reliance on the anaerobic pathways of ATP production which involves the hydrolysis of phosphocreatine (PCr) and anaerobic glycolysis. TFM may also damage the gills, which may disrupt gill-mediated ion regulation and cause internal ion imbalances. While knowledge of TFM toxicity in larval lampreys …

Improving Understanding Of Endocrine-Active Compounds In Pulp And Paper Mill Condensates Using A Mummichog (Fundulus Heteroclitus) Bioassay, Robert John Gary Rutherford

Theses and Dissertations (Comprehensive)

Since the late 1990s an investigation of cause (IOC) study at Irving Pulp and Paper Ltd (IPP), a bleached kraft mill in Saint John, NB, Canada, has successfully identified an in-mill waste stream (5th effect evaporator condensates) as containing endocrine disrupting substances (EDSs). These EDSs affect levels of reproductive steroids in a native estuarine fish, the mummichog (Fundulus heteroclitus). To confirm the minimal concentration at which whole condensates impact reproductive endpoints, adult mummichog were exposed to 2% and 4% (v/v) whole condensates for 14 days. Plasma testosterone was significantly depressed in males in the 4% (v/v) treatment, confirming …

Cd-Induced Responses In Plasma Ionic Regulation And Oxidative Stress In Rainbow Trout (O. Mykiss) Or Lake Whitefish (C. Clupeaformis) During Chronic Waterborne Exposure, Amanda Mancini

Theses and Dissertations (Comprehensive)

During chronic exposure to Cd or other metals, freshwater fish generally undergo physiological changes that results in acclimation, following a phase of damage and subsequent repair. The mechanisms associated with deleterious cellular effects induced by Cd throughout long-term exposures are less understood than those of acute toxicity, and may relate to an over-production of reactive oxygen species. The objectives of the present study were to examine the changes in, and relationship between, tissue-specific oxidative damage and antioxidant response, as well as plasma ionic regulation and tissue accumulation, in two freshwater salmonids throughout chronic Cd exposure. Rainbow trout (O. mykiss …

Linking Cd Accumulation And Effect In Resistant And Sensitive Freshwater Invertebrates, Tony Straus

Theses and Dissertations (Comprehensive)

There has been recent discussion within the field of environmental toxicology as to the viability of using the bioaccumulation of a chemical toxicant to predict toxic effects. Current literature has shown this concept to carry some merit, although there is a major flaw in that with many cases, namely those involving sensitive species, body burdens cannot be reliably linked to effects (Adams et al. (2010)). Bearing this issue in mind the goal of this thesis was to assess the viability of using bioaccumulation as a measure of effect in a different way.

The proposed idea utilized Cd accumulation in a …

The Evolution Of Sexual Reproduction In Cuscuta (Convolvulaceae), Michael Wright

Theses and Dissertations (Comprehensive)

Cuscuta (Convolvulaceae), the dodders, is a genus of ca. 200 species of obligate stem parasites distributed across a great diversity of habitats worldwide. The existence of a handful of species that are dangerous crop weeds has led researchers to historically focus on their growth and control. Consequently, there is a dearth of information about their biodiversity, ecology, and in particular their reproductive biology. This thesis surveys aspects of sex allocation, floral evolution, floral rewards for pollinators, and mechanisms of reproductive assurance across the genus. I demonstrate that Cuscuta has evolved a broad spectrum of breeding systems, from obligate selfing to …

Interface Between Black-Footed Ferret Research And Operational Conservation., Dean E. Biggins, Travis M. Livieri, Stewart W. Breck

United States Department of Agriculture Wildlife Services: Staff Publications

Questions and problems that emerged during operational conservation of black-footed ferrets (Mustela nigripes)have been addressed by a wide variety of studies. Early results from such studies often were communicated orally during meetings of recovery groups and in written form using memoranda, unpublished reports, and theses. Typically, implementation of results preceded their publication in widely distributed journals. Many of these studies eventually were published in journals, and we briefly summarize the contents of 8 volumes and special features of journals that have been dedicated to the biology of ferrets and issues in ferret recovery. This year marks the 30th anniversary of …

White-Tailed Deer Incidents With U.S. Civil Aircraft, Kirsten M. Biondi, Jerrold L. Belant, James A. Martin, Travis L. Devault, Guiming Wang

United States Department of Agriculture Wildlife Services: Staff Publications

Aircraft incidents with ungulates cause substantial economic losses and pose risks to human safety. We analyzed 879 white-tailed deer (Odocoileus virginianus) incidents with United States civil aircraft from 1990 to 2009 reported in the Federal Aviation Administration National Wildlife Strike Database. During that time, deer incidents followed a quadratic response curve, peaking in 1994 and declining thereafter. There appeared to be some seasonal patterning in incident frequency, with deer incidents increasing overall from January to November, and peaking in October and November (30.7%). Most incidents (64.8%) occurred at night, but incident rates were greatest (P 0.001) at dusk. Landing-roll represented …

Acetaminophen And Zinc Phosphide For Lethal Management Of Invasive Lizards Ctenosaura Similis , Michael L. Avery, John D. Eisemann, Kandy L. Keacher, Peter J. Savarie

United States Department of Agriculture Wildlife Services: Staff Publications

Reducing populations of invasive lizards through trapping and shooting is feasible in many cases but effective integrated management relies on a variety of tools, including toxicants. In Florida, using wild-caught non-native black spiny-tailed iguanas Ctenosaura similis, we screened acetaminophen and zinc phosphide to determine their suitability for effective population management of this prolific invasive species. Of the animals that received acetaminophen, none died except at the highest test dose, 240 mg per lizard, which is not practical for field use. Zinc phosphide produced 100% mortality at dose levels as little as 25 mg per lizard, equivalent to about 0.5% in …

Hair Of The Dog: Obtaining Samples From Coyotes And Wolves Noninvasively, David E. Ausband, Julie K. Young, Barbara Fannin, Michael S. Mitchell, Jennifer L. Stenglen, Lizette P. Waits, John A. Shivik

United States Department of Agriculture Wildlife Services: Staff Publications

Canids can be difficult to detect and their populations difficult to monitor. We tested whether hair samples could be collected from coyotes (Canis latrans) in Texas, USA and gray wolves (C. lupus) in Montana, USA using lure to elicit rubbing behavior at both man-made and natural collection devices. We usedmitochondrial and nuclearDNA to determine whether collected hair samples were from coyote, wolf, or nontarget species. Both coyotes and wolves rubbed on man-made barbed surfaces but coyotes in Texas seldom rubbed on hanging barbed surfaces. Wolves in Montana showed a tendency to rub at stations where natural material collection devices (sticks …

Modeling Connectivity Of Black Bears In A Desert Sky Island Archipelago, Todd C. Atwood, Julie K. Young, Jon P. Beckmann, Stewart W. Breck, Jennifer A. Fike, Olin E. Rhodes Jr., Kirby D. Bristow

United States Department of Agriculture Wildlife Services: Staff Publications

Landscape features such as rivers, mountains, desert basins, roads, and impermeable man-made structures may influence dispersal and gene flow among populations, thereby creating spatial structure across the landscape. In the US–Mexico borderland, urbanization and construction of the border fence have the potential to increase genetic subdivision and vulnerability to isolation in large mammal populations by bisecting movement corridors that have enabled dispersal between adjacent Sky Island mountain ranges. We examined genetic variation in black bears (Ursus americanus) from three regions in central and southern Arizona, US, to assess genetic and landscape connectivity in the US–Mexico border Sky Islands. We found …

Partitioning Of Anthropogenic Watering Sites By Desert Carnivores., Todd C. Atwood, Tricia L. Fry, Bruce Leland

United States Department of Agriculture Wildlife Services: Staff Publications

We investigated the role of water features as focal attractors for gray foxes (Urocyon cinereoargenteus), coyotes (Canis latrans), and bobcats (Felis rufus) in west Texas to determine if they were foci for interspecific interaction. Mixed effects models indicated that species partitioned use of water features spatially and temporally. Linear models indicated factors influencing relative activity at water features varied by species. For coyotes and bobcats, the water availability model, containing days since last rainfall and nearest-neighbor distance to water was best supported by the data, with relative activity increasing with time between rainfall and distance between waters. For gray foxes, …

Wild Dogma Ii: The Role And Implications Of Wild Dogma For Wild Dog Management In Australia., Benjamin L. Allen, Richard M. Engeman, Lee R. Allen

United States Department of Agriculture Wildlife Services: Staff Publications

The studies of Allen (2011) and Allen et al. (2011) recently examined the methodology underpinning claims that dingoes provide net benefits to biodiversity by suppressing foxes and cats. They found most studies to have design flaws and/or observational methods that preclude valid interpretations from the data, describing most of the current literature as ‘wild dogma’. In this short supplement, we briefly highlight the roles and implications of wild dogma for wild dog management in Australia. We discuss nomenclature, and the influence that unreliable science can have on policy and practice changes related to apex predator management

Wild Dogma: An Examination Of Recent "Evidence" For Dingo Regulation Of Invasive Mesopredator Release In Australia., Benjamin L. Allen, Richard M. Engeman, Lee R. Allen

United States Department of Agriculture Wildlife Services: Staff Publications

There is growing interest in the role that apex predators play in shaping terrestrial ecosystems and maintaining trophic cascades. In line with the mesopredator release hypothesis, Australian dingoes (Canis lupus dingo and hybrids) are assumed by many to regulate the abundance of invasive mesopredators, such as red foxes Vulpes vulpes and feral cats Felis catus, thereby providing indirect benefits to various threatened vertebrates. Several recent papers have claimed to provide evidence for the biodiversity benefits of dingoes in this way. Nevertheless, in this paper we highlight several critical weaknesses in the methodological approaches used in many of these reports, including …

Rock Pigeon Use Of Livestock Facilities In Northern Colorado: Implications For Improving Farm Bio-Security., James C. Carlson, Larry Clark, Michael F. Antolin, M. D. Salman

United States Department of Agriculture Wildlife Services: Staff Publications

Rock pigeons (Columba livia) have been implicated in the spread of pathogens within commercial livestock facilities. Currently, there is no data characterizing pigeon habitat use and movement patterns within and among commercial livestock facilities. To better understand the capacity for pigeons to spread pathogens, we used radio-telemetry techniques to estimate the home-range, travel distance, activity, and habitat use of pigeons roosting on and off dairies and feedlots in western Weld County, Colorado. Our observations suggest that pigeons roosting on (resident) and off (nonresident) livestock facilities use habitat differently. Nonresident pigeons used larger home-range areas than did resident pigeons. Nonresident pigeons …

Absence Of Mycobacterium Bovis In Feral Swine (Sus Scrofa) From The Southern Texas Border Region., Tyler A. Campbell, David B. Long, Luiz R. Bazan, Bruce V. Thomsen, Suelee Robbe-Austerman, Ronald B. Davey, Liza A. Soliz, Seth Swafford, Kurt C. Vercauteren

United States Department of Agriculture Wildlife Services: Staff Publications

Free-ranging wildlife, such as feral swine (Sus scrofa), harbor a variety of diseases that are transmissible to livestock and could negatively impact agricultural production. Information is needed regarding the exposure and infection rates of Mycobacterium bovis and many other diseases and parasites in feral swine occurring in the Texas border region. Our main objective was to determine exposure rates and possible infection rates of M. bovis in feral swine by opportunistically sampling animals from the Texas border region. From June to September 2010, we obtained samples from 396 feral swine and tested 98 samples for M. bovis by histopathology and …

Natal Colony Site Fidelity Of Herring Gulls At Sandusky Bay, Ohio., Bruce N. Buckingham, Benjamin Bacak

United States Department of Agriculture Wildlife Services: Staff Publications

We studied three Herring Gull (Larus argentatus) colonies in the Sandusky Bay area, Sandusky, OH, between 1981 and 2006. During this period, we banded 24,000 nestlings and received reports of 347 recovered bands. Forty-nine of these band recoveries were as adults recovered during the nesting season as far as 890 km from their natal colony. Gulls were also captured at five other colonies located in the Great Lakes. Gulls recovered outside the original 10-min block of banding accounted for 47 percent of the returns. We hypothesize that half of the recoveries of adult Herring Gulls during the nesting season occurred …

Domestic Calf Mortality And Producer Detection Rates In The Mexican Wolf Recovery Area: Implications For Livestock Management And Carnivore Compensation Schemes., Stewart W. Breck, Bryan M. Kluever, Michael Panasci, John Oakleaf, Terry Johnson, Warren B. Ballard, Larry Howery, David L. Bergman

United States Department of Agriculture Wildlife Services: Staff Publications

Conserving large carnivores throughout the world will often require that they share the landscape with livestock. Minimizing depredations and increasing tolerance by livestock producers will be critical for conservation efforts. To investigate factors influencing calf mortality and producer detection rates (i.e., number of livestock killed by predators, found by producers, and correctly classified as to cause of death), we monitored radio-tagged domestic calves at two sites in the Mexican wolf recovery area (East Eagle [EE] and Adobe Ranch [AR]). Study areas differed in grazing practices, density of predators (mountain lions, black bears, coyotes, and Mexican wolves), and amount of effort …

Testing The Terrain Hypothesis: Canada Geese See Their World Laterally And Obliquely, Esteban Fernández-Juricic, Bret A. Moore, Megan Doppler, Joseph Freeman, Bradley F. Blackwelll, Steven L. Lima, Travis L. Devault

United States Department of Agriculture Wildlife Services: Staff Publications

The distribution of ganglion cells in the retina determines the specific regions of the visual field with high visual acuity, and thus reflects the perception of a species’ visual environment. The terrain hypothesis proposes that animals living in open areas should have a horizontal visual streak across the retina with high ganglion cell density to increase visual acuity along the horizon. We tested this hypothesis in Canada geese (Branta canadensis) by assessing retinal topography, visual field configuration, and scanning behavior. We found that geese have an oblique rather than a horizontal visual streak across the retina: from a …

Cooperative And Antagonistic Roles For Heterochromatin Proteins In Transcriptional Regulation Of The Drosophila Sex Determination Masterswitch Gene, Hui Li

University of Kentucky Doctoral Dissertations

HOAP was originally identified as a component of an ORC-containing multi-protein complex of Heterochromatin Protein 1 (HP1) from early Drosophila embryos. HOAP immunostaining showed prominent association of it with telomeres, and mutants for HOAP (cav¹) showed it functions along with HP1 in forming a telomere capping complex that prevents telomeric fusions.

Weaker HOAP immunostaining is also observed in regions of pericentric heterochromatin and euchromatin. To examine the role of HOAP at these non-telomeric sites, we applied Affymetric Drosophila Genome Arrays to undertake a microarray expression profiling study of genes that are mis-expressed in cav¹ mutant larvae. The …

The Effects Of Nutritionally‐Modulated Prepartum Bcs On Pre‐ And Postpartum Metabolic Responses, In Vitro Lipid Metabolism And Performance Of Multiparous Beef Cows, Melissa Dale Hudson

University of Kentucky Doctoral Dissertations

Increased BCS at calving due to nutritional manipulation during the prepartum period resulted in greater mobilization of body fat after calving, regardless of plane of nutrition during the last 60 d of gestation. Although fatter cows were shown to have greater mobilization of reserves during the postpartum period, they maintained greater BCS at all points from calving to weaning compared to cows calving with fewer reserves at calving. A unique finding of this experiment was that the variation in BCS at calving was positively associated with BCS loss for cows fed to accrete BC during the prepartum period but was …

Comparison Of Digestive Function In Young And Mature Horses, Jennifer Elizabeth Earing

University of Kentucky Doctoral Dissertations

While forage plays an important role in equine nutrition, little research has been conducted evaluating fiber utilization by young horses. Therefore, studies were conducted to compare in vivo digestibility and digesta passage in weanlings and mature horses (Exp 1) and yearlings and mature horses (Exp 2). All horses were fed forage-based diets at the same rate (on a metabolic BW basis; Exp 1: 67% alfalfa cubes, 33% concentrate; Exp 2: 75% timothy cubes, 25% concentrate). Ytterbium labeled hay and cobalt-ethylenediaminetetraacetic acid were used to estimate digesta mean retention time (MRT), while in vivo digestibility (DM, OM, and NDF) was measured …

Effects Of Corticosterone And Ethanol Co-Exposure On Hippocampal Toxicity: Potential Role For The Nmda Nr2b Subunit, Tracy Renee Butler

University of Kentucky Doctoral Dissertations

Chronic ethanol (EtOH) exposure produces neuroadaptations within the NMDA receptor system and alterations in HPA axis functioning that contribute to neurodegeneration during ethanol withdrawal (EWD). Chronic EtOH exposure and EWD, as well as corticosteroids, also promote increased synthesis and release of polyamines, which allosterically potentiate NMDA receptor open-channel time at the NR2B subunit. The current studies investigated effects of 10 day EtOH and corticosterone (CORT) co-exposure on toxicity during EWD in rat organotypic hippocampal slice cultures, and alterations in function and/or density of the NR2B subunit of the NMDA receptor that may mediate CORT-potentiation of toxicity during EWD. We hypothesized …

Differential Innate Immune Responses Correlate With The Contrasting Pathogenicity Of The Equine H7n7 Influenza Virus Demonstrated In Horses And Balb/C Mice, Liang Zhang

University of Kentucky Doctoral Dissertations

Equine influenza virus causes a mild, self-limiting upper respiratory disease in its natural host. In stark contrast, equine influenza viruses of the H7N7 subtype produce lethal infection in BALB/c mice. This dissertation explored the mechanism underlying the differential pathogenicity of the equine H7N7 influenza virus observed in horses and BALB/c mice. Initially, a comparative study of the pathogenesis was conducted in BALB/c mice inoculated intranasally with a representative isolate of either H7N7 or H3N8 subtype equine influenza virus. All H3N8 virus-infected mice survived the infection whereas 100% mortality was documented for the mice receiving the H7N7 virus by day 8 …

Gene Expression Regulators Lin-11 And Let-711, In Modulating The Rate Of Aging And Lifespan, In C. Elegans., Tseten Yeshi Jamling

University of Kentucky Doctoral Dissertations

lin-11 and let-711 are early-developmental gene expression regulators with no previously known roles in aging regulation. Yet, they show strong aging-correlated expression profiles (Lund, Tedesco et al. 2002). lin-11 is strongly upregulated in very old worm populations, and let-711 is progressively downregulated in aging worm populations. Microarray studies were performed to identify their genome-wide targets, which were then subjected to further lifespan and genetic analysis to investigate their role in C. elegans aging.

The results indicate that the target pools of both lin-11 and let-711 are enriched for aging genes, since a significant number of tested genes increased lifespan. This …

Biological Control Of The Black Cutworm, Agrotis Ipsilon (Lepidoptera: Noctuidae), And Endophyte Mediated Tritrophic Interactions In Turfgrass, Andrea Jeanne Bixby-Brosi

University of Kentucky Doctoral Dissertations

Components of successful pest management programs must be complementary and not antagonistic. This project examined interactions between natural enemies of the black cutworm, Agrotis ipsilon (Hufnagel), an important turfgrass pest, and host plant resistance by endophytic grass.

Agrotis ipsilon nucleopolyhedrovirus (AgipMNPV) was examined as a bio-insecticide for controlling A. ipsilon in turfgrass. Fresh (1-week-old) AgipMNPV residues killed 76−86% of neonates hatching from eggs on golf course tees, however, residual control of implanted larvae lasted no more than a few weeks. Combinations of AgipMNPV with adjuvants, such as optical brightener and lignin, failed to accelerate or extend …

Engineering Proteins With Unique Characteristics For Diagnostics And Biosensors, Smita Joel

University of Kentucky Doctoral Dissertations

Proteins possess a broad range of structural and functional properties and, therefore, can be employed in a variety of biomedical applications. While a good number of protein-based biosensing systems and biosensors for target analytes have been developed, the search for versatile, highly sensitive and selective sensors with long term stability able to provide fast detection of target analytes continues to be a challenge. To that end, we now report the design and development of modified proteins with tailored characteristics and their further utilization in the development of biosensing systems.

We take advantage of binding proteins that undergo a change in …