Digital Commons Network^™

Aging Influences The Neural Correlates Of Lexical Decision But Not Automatic Semantic Priming, Brian T. Gold, Anders H. Andersen, Greg A. Jicha, Charles D. Smith

Neuroscience Faculty Publications

Human behavioral data indicate that older adults are slower to perform lexical decisions (LDs) than young adults but show similar reaction time gains when these decisions are primed semantically. The present study explored the functional neuroanatomic bases of these frequently observed behavioral findings. Young and older groups completed unprimed and primed LD tasks while functional magnetic resonance imaging (fMRI) was recorded, using a fully randomized trial design paralleling those used in behavioral research. Results from the unprimed task found that age-related slowing of LD was associated with decreased activation in perceptual extrastriate regions and increased activation in regions associated with …

Tumor Necrosis Factor-Alpha (Tnf-Α) Enhances Functional Thermal And Chemical Responses Of Trp Cation Channels In Human Synoviocytes, Mikhail Y. Kochukov, Terry A. Mcnearney, Huaizhi Yin, Liping Zhang, Fei Ma, Larissa Ponomareva, Sarah Abshire, Karin N. Westlund

Physiology Faculty Publications

Background: We have shown functional expression of several TRP channels on human synovial cells, proposing significance in known calcium dependent proliferative and secretory responses in joint inflammation. The present study further characterizes synoviocyte TRP expression and activation responses to thermal and osmotic stimuli after pre-treatment with proinflammatory mediator tumor necrosis factor alpha (TNF-α, EC50 1.3221 x 10^-10 g/L).

Results: Fluorescent imaging of Fura-2 loaded human SW982 synoviocytes reveals immediate and delayed cytosolic calcium oscillations elicited by (1) TRPV1 agonists capsaicin and resiniferatoxin (20-40% of cells), (2) moderate and noxious temperature change, and (3) osmotic stress TRPV4 activation (11.5% of …

Conservation Of The Glucan Phosphatase Laforin Is Linked To Rates Of Molecular Evolution And The Glucan Metabolism Of The Organism, Matthew S. Gentry, Rachel M. Pace

Molecular and Cellular Biochemistry Faculty Publications

BACKGROUND: Lafora disease (LD) is a fatal autosomal recessive neurodegenerative disease. A hallmark of LD is cytoplasmic accumulation of insoluble glucans, called Lafora bodies (LBs). Mutations in the gene encoding the phosphatase laforin account for approximately 50% of LD cases, and this gene is conserved in all vertebrates. We recently demonstrated that laforin is the founding member of a unique class of phosphatases that dephosphorylate glucans.

RESULTS: Herein, we identify laforin orthologs in a protist and two invertebrate genomes, and report that laforin is absent in the vast majority of protozoan genomes and it is lacking in all other invertebrate …

Human Cerebral Neuropathology Of Type 2 Diabetes Mellitus, Peter T. Nelson, Charles D. Smith, Erin L. Abner, Frederick A. Schmitt, Stephen W. Scheff, Gregory J. Davis, Jeffrey N. Keller, Gregory A. Jicha, Daron Davis, Wang-Xia Wang, Adria Hartman, Douglas G. Katz, William R. Markesbery

Pathology and Laboratory Medicine Faculty Publications

The cerebral neuropathology of Type 2 diabetes (CNDM2) has not been positively defined. This review includes a description of CNDM2 research from before the ‘Pubmed Era’. Recent neuroimaging studies have focused on cerebrovascular and white matter pathology. These and prior studies about cerebrovascular histopathology in diabetes are reviewed. Evidence is also described for and against the link between CNDM2 and Alzheimer's disease pathogenesis. To study this matter directly, we evaluated data from University of Kentucky Alzheimer's Disease Center (UK ADC) patients recruited while non-demented and followed longitudinally. Of patients who had come to autopsy (N = 234), 139 met …

Characterization Of Conserved Properties Of Hemagglutinin Of H5n1 And Human Influenza Viruses: Possible Consequences For Therapy And Infection Control, Veljko Veljkovic, Nevena Veljkovic, Claude P. Muller, Sybille Müller, Sanja Glisic, Vladimir Perovic, Heinz Köhler

Microbiology, Immunology, and Molecular Genetics Faculty Publications

BACKGROUND: Epidemics caused by highly pathogenic avian influenza virus (HPAIV) are a continuing threat to human health and to the world's economy. The development of approaches, which help to understand the significance of structural changes resulting from the alarming mutational propensity for human-to-human transmission of HPAIV, is of particularly interest. Here we compare informational and structural properties of the hemagglutinin (HA) of H5N1 virus and human influenza virus subtypes, which are important for the receptor/virus interaction.

RESULTS: Presented results revealed that HA proteins encode highly conserved information that differ between influenza virus subtypes H5N1, H1N1, H3N2, H7N7 and defined an …

Polyglutamine Disruption Of The Huntingtin Exon 1 N Terminus Triggers A Complex Aggregation Mechanism, Ashwani K. Thakur, Murali Jayaraman, Rakesh Mishra, Monika Thakur, Veronique M. Chellgren, In-Ja L Byeon, Dalaver H. Anjum, Ravindra Kodali, Trevor P. Creamer, James F. Conway, Angela M. Gronenborn, Ronald Wetzel

Molecular and Cellular Biochemistry Faculty Publications

Simple polyglutamine (polyQ) peptides aggregate in vitro via a nucleated growth pathway directly yielding amyloid-like aggregates. We show here that the 17-amino-acid flanking sequence (HTT^NT) N-terminal to the polyQ in the toxic huntingtin exon 1 fragment imparts onto this peptide a complex alternative aggregation mechanism. In isolation, the HTT^NT peptide is a compact coil that resists aggregation. When polyQ is fused to this sequence, it induces in HTT^NT, in a repeat-length dependent fashion, a more extended conformation that greatly enhances its aggregation into globular oligomers with HTT^NT cores and exposed polyQ. In a second …

The Future (Or Lack Of Future) Of Personalized Prescription In Psychiatry, Jose De Leon

Psychiatry Faculty Publications

Rapid technological advances in genetics have created conceptual chaos regarding the genetics of drug response. Terms for differing concepts are used interchangeably: pharmacogenetics with pharmacogenomics, personalized medicine with personalized prescription. Biomarker has many definitions. The author prefers the concept of personalized prescription and uses it with implications beyond pharmacogenetics by considering all scientific information valid for prescribing medication. Genetics may not be crucial for all drugs. In this comprehensive view, clinicians must consider genetic, environmental and personal variables when prescribing medication and incorporate some basic pharmacological principles: (1) safety and efficacy, (2) pharmacokinetics and pharmacodynamics, (3) therapeutic window and prescriber's …

Genic Regions Of A Large Salamander Genome Contain Long Introns And Novel Genes, Jeramiah J. Smith, Srikrishna Putta, Wei Zhu, Gerald M. Pao, Inder M. Verma, Tony Hunter, Susan V. Bryant, David M. Gardiner, Timothy T. Harkins, S. Randal Voss

Biology Faculty Publications

BACKGROUND: The basis of genome size variation remains an outstanding question because DNA sequence data are lacking for organisms with large genomes. Sixteen BAC clones from the Mexican axolotl (Ambystoma mexicanum: c-value = 32 x 10(9) bp) were isolated and sequenced to characterize the structure of genic regions.

RESULTS: Annotation of genes within BACs showed that axolotl introns are on average 10x longer than orthologous vertebrate introns and they are predicted to contain more functional elements, including miRNAs and snoRNAs. Loci were discovered within BACs for two novel EST transcripts that are differentially expressed during spinal cord regeneration and skin …