The University of Kentucky is a public co-educational university in Lexington, Kentucky. Founded in 1865 by John Bowman as the Agricultural and Mechanical College of Kentucky, the university is one of the state's two land-grant universities, the largest college or university in the state, with 28,928 students as of Fall 2012, and the highest ranked research university in the state according to U.S. News and World Report.The institution comprises 16 colleges, a graduate school, 93 undergraduate programs, 99 master programs, 66 doctoral programs, and four professional programs. The University of Kentucky has fifteen libraries on campus. The largest is William T. Young Library, a federal depository, hosting subjects related to social science, humanities and life science collections. In recent years, the university has focused expenditures increasingly on research, following a compact formed by the Kentucky General Assembly in 1997. The directive mandated that the university become a Top 20 public research institution, in terms of an overall ranking to be determined by the university itself, by the year 2020. Wikipedia.
Horbinski C.,University of Kentucky
Acta Neuropathologica | Year: 2013
Whole genome analyses have facilitated the discovery of clinically relevant genetic alterations in a variety of diseases, most notably cancer. A prominent example of this was the discovery of mutations in isocitrate dehydrogenases 1 and 2 (IDH1/2) in a sizeable proportion of gliomas and some other neoplasms. Herein the normal functions of these enzymes, how the mutations alter their catalytic properties, the effects of their D-2-hydroxyglutarate metabolite, technical considerations in diagnostic neuropathology, implications about prognosis and therapeutic considerations, and practical applications and controversies regarding IDH1/2 mutation testing are discussed. © Springer-Verlag Berlin Heidelberg 2013.
Elitzur M.,University of Kentucky
Astrophysical Journal Letters | Year: 2012
The inevitable spread in properties of the toroidal obscuration of active galactic nuclei (AGNs) invalidates the widespread notion that type 1 and 2 AGNs are intrinsically the same objects, drawn randomly from the distribution of torus covering factors. Instead, AGNs are drawn preferentially from the distribution; type 2 are more likely drawn from the distribution higher end, type 1 from its lower end. Type 2 AGNs have a higher IR luminosity, lower narrow-line luminosity, and a higher fraction of Compton thick X-ray obscuration than type 1. Meaningful studies of unification statistics cannot be conducted without first determining the intrinsic distribution function of torus covering factors. © 2012. The American Astronomical Society. All rights reserved.
Miller A.-F.,University of Kentucky
FEBS Letters | Year: 2012
Superoxide dismutases (SODs) catalyze the de toxification of superoxide. SODs therefore acquired great importance as O 2 became prevalent following the evolution of oxygenic photosynthesis. Thus the three forms of SOD provide intriguing insights into the evolution of the organisms and organelles that carry them today. Although ancient organisms employed Fe-dependent SODs, oxidation of the environment made Fe less bio-available, and more dangerous. Indeed, modern lineages make greater use of homologous Mn-dependent SODs. Our studies on the Fe-substituted MnSOD of Escherichia coli, as well as redox tuning in the FeSOD of E. coli shed light on how evolution accommodated differences between Fe and Mn that would affect SOD performance, in SOD proteins whose activity is specific to one or other metal ion. © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Murphy M.P.,University of Kentucky
Acta neuropathologica communications | Year: 2014
Mid-life obesity and type 2 diabetes mellitus (T2DM) confer a modest, increased risk for Alzheimer's disease (AD), though the underlying mechanisms are unknown. We have created a novel mouse model that recapitulates features of T2DM and AD by crossing morbidly obese and diabetic db/db mice with APPΔNL/ΔNLx PS1P264L/P264L knock-in mice. These mice (db/AD) retain many features of the parental lines (e.g. extreme obesity, diabetes, and parenchymal deposition of β-amyloid (Aβ)). The combination of the two diseases led to additional pathologies-perhaps most striking of which was the presence of severe cerebrovascular pathology, including aneurysms and small strokes. Cortical Aβ deposition was not significantly increased in the diabetic mice, though overall expression of presenilin was elevated. Surprisingly, Aβ was not deposited in the vasculature or removed to the plasma, and there was no stimulation of activity or expression of major Aβ-clearing enzymes (neprilysin, insulin degrading enzyme, or endothelin-converting enzyme). The db/AD mice displayed marked cognitive impairment in the Morris Water Maze, compared to either db/db or APPΔNLx PS1P264L mice. We conclude that the diabetes and/or obesity in these mice leads to a destabilization of the vasculature, leading to strokes and that this, in turn, leads to a profound cognitive impairment and that this is unlikely to be directly dependent on Aβ deposition. This model of mixed or vascular dementia provides an exciting new avenue of research into the mechanisms underlying the obesity-related risk for age-related dementia, and will provide a useful tool for the future development of therapeutics.
Wang K.,University of Kentucky
Nucleic acids research | Year: 2010
The accurate mapping of reads that span splice junctions is a critical component of all analytic techniques that work with RNA-seq data. We introduce a second generation splice detection algorithm, MapSplice, whose focus is high sensitivity and specificity in the detection of splices as well as CPU and memory efficiency. MapSplice can be applied to both short (<75 bp) and long reads (≥ 75 bp). MapSplice is not dependent on splice site features or intron length, consequently it can detect novel canonical as well as non-canonical splices. MapSplice leverages the quality and diversity of read alignments of a given splice to increase accuracy. We demonstrate that MapSplice achieves higher sensitivity and specificity than TopHat and SpliceMap on a set of simulated RNA-seq data. Experimental studies also support the accuracy of the algorithm. Splice junctions derived from eight breast cancer RNA-seq datasets recapitulated the extensiveness of alternative splicing on a global level as well as the differences between molecular subtypes of breast cancer. These combined results indicate that MapSplice is a highly accurate algorithm for the alignment of RNA-seq reads to splice junctions. Software download URL: http://www.netlab.uky.edu/p/bioinfo/MapSplice.