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University of Kentucky

2011

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Effects Of Response Elaboration Training On Sentence Production Of Persons With Chronic Agrammatic Aphasia, Ryan S. Husak Dec 2011

Effects Of Response Elaboration Training On Sentence Production Of Persons With Chronic Agrammatic Aphasia, Ryan S. Husak

Theses and Dissertations--Rehabilitation Sciences

Purpose: Response Elaboration Training (RET) is a treatment program for increasing the amount of information contained in the speech of individuals with aphasia. This study employed a sentence production task (SPT) to examine whether RET will (1) generalize to a task not worked on in treatment and (2) affect syntactic performance.

Methods and Procedures: Three adults with chronic non-fluent Broca’s aphasia received RET in this prospective, repeated case study. The dependent variable was a SPT requiring the participant to put a verb in a sentence. Changes in the syntactic performance of the participant’s sentence productions were classified across …


A Shared Gene Expression Signature In Mouse Models Of Ebv-Associated And Non-Ebv-Associated Burkitt Lymphoma, Kathryn T. Bieging, Kamonwan Fish, Subbarao Bondada, Richard Longnecker Dec 2011

A Shared Gene Expression Signature In Mouse Models Of Ebv-Associated And Non-Ebv-Associated Burkitt Lymphoma, Kathryn T. Bieging, Kamonwan Fish, Subbarao Bondada, Richard Longnecker

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The link between EBV infection and Burkitt lymphoma (BL) is strong, but the mechanism underlying that link has been elusive. We have developed a mouse model for EBV-associated BL in which LMP2A, an EBV latency protein, and MYC are expressed in B cells. Our model has demonstrated the ability of LMP2A to accelerate tumor onset, increase spleen size, and bypass p53 inactivation. Here we describe the results of total gene expression analysis of tumor and pretumor B cells from our transgenic mouse model. Although we see many phenotypic differences and changes in gene expression in pretumor B cells, the transcriptional …


Microglial P38Α Mapk Is Critical For Lps-Induced Neuron Degeneration, Through A Mechanism Involving Tnfα, Bin Xing, Adam D. Bachstetter, Linda J. Van Eldik Dec 2011

Microglial P38Α Mapk Is Critical For Lps-Induced Neuron Degeneration, Through A Mechanism Involving Tnfα, Bin Xing, Adam D. Bachstetter, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: The p38α MAPK isoform is a well-established therapeutic target in peripheral inflammatory diseases, but the importance of this kinase in pathological microglial activation and detrimental inflammation in CNS disorders is less well understood. To test the role of the p38α MAPK isoform in microglia-dependent neuron damage, we used primary microglia from wild-type (WT) or p38α MAPK conditional knockout (KO) mice in co-culture with WT cortical neurons, and measured neuron damage after LPS insult.

RESULTS: We found that neurons in co-culture with p38α-deficient microglia were protected against LPS-induced synaptic loss, neurite degeneration, and neuronal death. The involvement of the proinflammatory …


Synergistic Roles Of Eukaryotic Translation Elongation Factors 1bγ And 1a In Stimulation Of Tombusvirus Minus-Strand Synthesis, Zsuzsanna Sasvari, Lara Izotova, Terri Goss Kinzy, Peter D. Nagy Dec 2011

Synergistic Roles Of Eukaryotic Translation Elongation Factors 1bγ And 1a In Stimulation Of Tombusvirus Minus-Strand Synthesis, Zsuzsanna Sasvari, Lara Izotova, Terri Goss Kinzy, Peter D. Nagy

Plant Pathology Faculty Publications

Host factors are recruited into viral replicase complexes to aid replication of plus-strand RNA viruses. In this paper, we show that deletion of eukaryotic translation elongation factor 1Bgamma (eEF1Bγ) reduces Tomato bushy stunt virus (TBSV) replication in yeast host. Also, knock down of eEF1Bγ level in plant host decreases TBSV accumulation. eEF1Bγ binds to the viral RNA and is one of the resident host proteins in the tombusvirus replicase complex. Additional in vitro assays with whole cell extracts prepared from yeast strains lacking eEF1Bγ demonstrated its role in minus-strand synthesis by opening of the structured 3' end of the viral …


Driving Qi With Research: Findings From Public Health Pbrns, Glen P. Mays Dec 2011

Driving Qi With Research: Findings From Public Health Pbrns, Glen P. Mays

Health Management and Policy Presentations

Public health agencies are increasingly experimenting with quality improvement (QI) strategies designed to enhance the effectiveness and efficiency of their efforts. Does QI work in public health, and if so for whom and under what circumstances? What QI strategies work best for which types of public health process failures, and at what cost? Research underway through the Public Health Practice-Based Research Networks (PBRN) Program is examining these types of questions to build an evidence base for public health QI.


Project P.A.T.H.S. In Hong Kong: New Curriculum In Response To Adolescent Developmental Issues, Hing Keung Ma, Daniel T. L. Shek, Joav Merrick Dec 2011

Project P.A.T.H.S. In Hong Kong: New Curriculum In Response To Adolescent Developmental Issues, Hing Keung Ma, Daniel T. L. Shek, Joav Merrick

Pediatrics Faculty Publications

No abstract.


Juvenile Hormone Regulates Vitellogenin Gene Expression Through Insulin-Like Peptide Signaling Pathway In The Red Flour Beetle, Tribolium Castaneum, Zhentao Sheng, Jingjing Xu, Hua Bai, Fang Zhu, Subba R. Palli Dec 2011

Juvenile Hormone Regulates Vitellogenin Gene Expression Through Insulin-Like Peptide Signaling Pathway In The Red Flour Beetle, Tribolium Castaneum, Zhentao Sheng, Jingjing Xu, Hua Bai, Fang Zhu, Subba R. Palli

Entomology Faculty Publications

Our recent studies identified juvenile hormone (JH) and nutrition as the two key signals that regulate vitellogenin (Vg) gene expression in the red flour beetle, Tribolium castaneum. Juvenile hormone regulation of Vg synthesis has been known for a long time in several insects, but the mechanism of JH action is not known. Experiments were conducted to determine the mechanism of action of these two signals in regulation of Vg gene expression. Injection of bovine insulin or FOXO double-stranded RNA into the previtellogenic, starved, or JH-deficient female adults increased Vg mRNA and protein levels, thereby implicating the pivotal role for …


Effect Of Duration And Amplitude Of Direct Current When Lidocaine Is Delivered By Iontophoresis, Susan A. Saliba, Courtney L. Teeter-Heyl, Patrick O. Mckeon, Christopher D. Ingeroll, Ethan N. Saliba Dec 2011

Effect Of Duration And Amplitude Of Direct Current When Lidocaine Is Delivered By Iontophoresis, Susan A. Saliba, Courtney L. Teeter-Heyl, Patrick O. Mckeon, Christopher D. Ingeroll, Ethan N. Saliba

Physical Therapy Faculty Publications

Dosage for the galvanic stimulation for iontophoresis varies. Clinicians manipulate the duration or the amplitude of the current, but it is not known which is more effective. We compared the anesthetic effect of lidocaine HCL (2%) by manipulating the current parameters on 21 healthy volunteers (age: 21.2 ± 4.2, height 170.7 ± 10.2 cm, mass 82.1 ± 19.2 kg). Three conditions were administered in a random order using a Phoresor II® with 2 mL, 2% lidocaine HCL in an iontophoresis electrode. (1) HASD (40 mA*min): High amplitude (4 mA), short duration (10 min); (2) LALD (40 mA.min): …


Acrb Trimer Stability And Efflux Activity, Insight From Mutagenesis Studies, Linliang Yu, Wei Lu, Yinan Wei Dec 2011

Acrb Trimer Stability And Efflux Activity, Insight From Mutagenesis Studies, Linliang Yu, Wei Lu, Yinan Wei

Chemistry Faculty Publications

The multidrug transporter AcrB in Escherichia coli exists and functions as a homo-trimer. The assembly process of obligate membrane protein oligomers, including AcrB, remains poorly understood. In a previous study, we have shown that individual AcrB subunit is capable of folding independently, suggesting that trimerization of AcrB follows a three-stage pathway in which monomers first fold, and then assemble. Here we destabilized the AcrB trimer through mutating a single Pro (P223) in the protruding loop of AcrB, which drastically reduced the protein activity. We replaced P223 separately with five residues, including Ala, Val, Tyr, Asn, and Gly, and found that …


Maternal Separation Affects Dopamine Transporter Function In The Spontaneously Hypertensive Rat: An In Vivo Electrochemical Study, Jacqueline S. Womersley, Jennifer H. Hsieh, Lauriston A. Kellaway, Greg A. Gerhardt, Vivienne A. Russell Dec 2011

Maternal Separation Affects Dopamine Transporter Function In The Spontaneously Hypertensive Rat: An In Vivo Electrochemical Study, Jacqueline S. Womersley, Jennifer H. Hsieh, Lauriston A. Kellaway, Greg A. Gerhardt, Vivienne A. Russell

Neuroscience Faculty Publications

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a developmental disorder characterised by symptoms of inattention, impulsivity and hyperactivity. The spontaneously hypertensive rat (SHR) is a well-characterised model of this disorder and has been shown to exhibit dopamine dysregulation, one of the hypothesised causes of ADHD. Since stress experienced in the early stages of life can have long-lasting effects on behaviour, it was considered that early life stress may alter development of the dopaminergic system and thereby contribute to the behavioural characteristics of SHR. It was hypothesized that maternal separation would alter dopamine regulation by the transporter (DAT) in ways that distinguish SHR …


Comparison Of Hip And Knee Strength And Neuromuscular Activity In Subjects With And Without Patellofemoral Pain Syndrome, Lori Ann Bolgla, Terry R. Malone, Brian R. Umberger, Timothy L. Uhl Dec 2011

Comparison Of Hip And Knee Strength And Neuromuscular Activity In Subjects With And Without Patellofemoral Pain Syndrome, Lori Ann Bolgla, Terry R. Malone, Brian R. Umberger, Timothy L. Uhl

Physical Therapy Faculty Publications

Purpose/Background: Historically, patellofemoral pain syndrome (PFPS) has been viewed exclusively as a knee problem. Recent findings have suggested an association between hip muscle weakness and PFPS. Altered neuromuscular activity about the hip also may contribute to PFPS; however, more limited data exist regarding this aspect. Most prior investigations also have not concurrently examined hip and knee strength and neuromuscular activity in this patient population. Additional knowledge regarding the interaction between hip and knee muscle function may enhance the current understanding of PFPS. The purpose of this study was to compare hip and knee strength and electromyographic (EMG) …


Adipose Tissue Extracellular Matrix And Vascular Abnormalities In Obesity And Insulin Resistance, Michael Spencer, Resat Unal, Beibei Zhu, Neda Rasouli, Robert E. Mcgehee Jr., Charlotte A. Peterson, Philip A. Kern Dec 2011

Adipose Tissue Extracellular Matrix And Vascular Abnormalities In Obesity And Insulin Resistance, Michael Spencer, Resat Unal, Beibei Zhu, Neda Rasouli, Robert E. Mcgehee Jr., Charlotte A. Peterson, Philip A. Kern

Clinical and Translational Science Faculty Publications

Context: Insulin resistance is associated with inflammation, fibrosis, and hypoxia in adipose tissue.

Objective: This study was intended to better characterize the extracellular matrix (ECM) and vascularity of insulin-resistant adipose tissue. Design: Adipose expression of collagens, elastin, and angiogenic factors was assessed using realtime RT-PCR and immunohistochemistry (IHC) in abdominal sc adipose tissue. Adipocyte-macrophage coculture experiments examined the effects of polarized macrophages on adipose ECM gene expression, and the effects of collagens were measured in an angiogenesis assay.

Participants and Setting: A total of 74 nondiabetic subjects participated at a University Clinical Research Center. Interventions: Interventions included baseline adipose biopsy …


Widespread Regulation Of Mirna Biogenesis At The Dicer Step By The Cold-Inducible Rna-Binding Protein, Rbm3, Julie Pilotte, Esther E. Dupont-Versteegden, Peter W. Vanderklish Dec 2011

Widespread Regulation Of Mirna Biogenesis At The Dicer Step By The Cold-Inducible Rna-Binding Protein, Rbm3, Julie Pilotte, Esther E. Dupont-Versteegden, Peter W. Vanderklish

Physical Therapy Faculty Publications

MicroRNAs (miRNAs) play critical roles in diverse cellular events through their effects on translation. Emerging data suggest that modulation of miRNA biogenesis at post-transcriptional steps by RNA-binding proteins is a key point of regulatory control over the expression of some miRNAs and the cellular processes they influence. However, the extent and conditions under which the miRNA pathway is amenable to regulation at posttranscriptional steps are poorly understood. Here we show that RBM3, a cold-inducible, developmentally regulated RNA-binding protein and putative protooncogene, is an essential regulator of miRNA biogenesis. Utilizing miRNA array, Northern blot, and PCR methods, we observed that over …


A Comparison Of Intensive Care Unit Mortality Prediction Models Through The Use Of Data Mining Techniques, Sujin Kim, Woojae Kim, Rae Woong Park Dec 2011

A Comparison Of Intensive Care Unit Mortality Prediction Models Through The Use Of Data Mining Techniques, Sujin Kim, Woojae Kim, Rae Woong Park

Institute for Biomedical Informatics Faculty Publications

OBJECTIVES: The intensive care environment generates a wealth of critical care data suited to developing a well-calibrated prediction tool. This study was done to develop an intensive care unit (ICU) mortality prediction model built on University of Kentucky Hospital (UKH)'s data and to assess whether the performance of various data mining techniques, such as the artificial neural network (ANN), support vector machine (SVM) and decision trees (DT), outperform the conventional logistic regression (LR) statistical model.

METHODS: The models were built on ICU data collected regarding 38,474 admissions to the UKH between January 1998 and September 2007. The first 24 hours …


Forage News [2011-12], Department Of Plant And Soil Sciences, University Of Kentucky Dec 2011

Forage News [2011-12], Department Of Plant And Soil Sciences, University Of Kentucky

Forage News

  • Heart of America Grazing Conference
  • UK Forage Variety Tests
  • Forage Dynamics and Calf Behavior in Two Creep Grazing Systems
  • Testing and Feeding Tobacco-Brown Hay and Silage
  • World Population Hits Seven Billion
  • Farmers Use of Broadband Internet
  • High Cattle Prices to Continue, Analysts Say


Federalizing Medicaid, Nicole Huberfeld Dec 2011

Federalizing Medicaid, Nicole Huberfeld

Law Faculty Scholarly Articles

This Article is one of only a small number of proposals over the past forty-six years for federalizing Medicaid. None of these proposals has grappled directly with the reasons that Medicaid does not satisfy federalism goals, and thus a key reason for modernizing Medicaid’s structure has been ignored. Despite being an area of “traditional state concern,” healthcare should no longer be left to the economic and political whims of the states, as Medicaid is not an effective Brandeisian “laboratory of the states.” Admittedly, some would oppose centralization on the ideological grounds that more federal government power is bad, and more …


Liposomal, Ring-Opened Camptothecins With Prolonged, Site-Specific Delivery Of Active Drug To Solid Tumors, Bradley D. Anderson, Vijay Joguparthi, Tiang-Xiang Xiang Nov 2011

Liposomal, Ring-Opened Camptothecins With Prolonged, Site-Specific Delivery Of Active Drug To Solid Tumors, Bradley D. Anderson, Vijay Joguparthi, Tiang-Xiang Xiang

Pharmaceutical Sciences Faculty Patents

A method for preparing a stable dispersion of a camptothecin, camptothecin prodrug, or analog thereof for administration to a patient in need thereof includes preparing a solution of the camptothecin, wherein the solution has a pH which places substantially an entirety of that camptothecin in a carboxylate form. The camptothecin may be a neutral camptothecin. The solution is next loaded into a liposome including at least one lipid, which may be a phospholipid. An intraliposomal pH is maintained which preserves substantially an entirety of the camptothecin in the carboxylate form. The liposomal dispersion is administered to an individual in need …


Autoimmune Enteropathy With A Cd8+ Cd7- T-Cell Small Bowel Intraepithelial Lymphocytosis: Case Report And Literature Review, Shrinivas Bishu, Violeta Arsenescu, Eun Y. Lee, H. David Vargas, Willem J. S. De Villiers, Razvan Arsenescu Nov 2011

Autoimmune Enteropathy With A Cd8+ Cd7- T-Cell Small Bowel Intraepithelial Lymphocytosis: Case Report And Literature Review, Shrinivas Bishu, Violeta Arsenescu, Eun Y. Lee, H. David Vargas, Willem J. S. De Villiers, Razvan Arsenescu

Surgery Faculty Publications

Background

Adult onset autoimmune enteropathy (AIE) is a rare condition characterized by diarrhea refractory to dietary therapy diagnosed in patients with evidence of autoimmune conditions. Auto-antibodies to gut epithelial cells and other tissues are commonly demonstrated. Despite increasing awareness, the pathogenesis, histologic, immunologic and clinical features of AIE remain uncertain. There remains controversy regarding the diagnostic criteria, the frequency and types of auto-antibodies and associated autoimmune conditions, and the extent and types of histologic and immunologic abnormalities. CD4+ T-cells are thought to at least responsible for this condition; whether other cell types, including B- and other T-cell subsets are involved, …


Exploration And Comparison Of Methods For Combining Population- And Family-Based Genetic Association Using The Genetic Analysis Workshop 17 Mini-Exome, David W. Fardo, Anthony R. Druen, Jinze Liu, Lucia Mirea, Claire Infante-Rivard, Patrick Breheny Nov 2011

Exploration And Comparison Of Methods For Combining Population- And Family-Based Genetic Association Using The Genetic Analysis Workshop 17 Mini-Exome, David W. Fardo, Anthony R. Druen, Jinze Liu, Lucia Mirea, Claire Infante-Rivard, Patrick Breheny

Biostatistics Faculty Publications

We examine the performance of various methods for combining family- and population-based genetic association data. Several approaches have been proposed for situations in which information is collected from both a subset of unrelated subjects and a subset of family members. Analyzing these samples separately is known to be inefficient, and it is important to determine the scenarios for which differing methods perform well. Others have investigated this question; however, no extensive simulations have been conducted, nor have these methods been applied to mini-exome-style data such as that provided by Genetic Analysis Workshop 17. We quantify the empirical power and false-positive …


Removing Aluminum From Solution Using Chelating Compounds And Immobilized Tethered Chelators, Robert A. Yokel, Wesley R. Harris, Christopher D. Spilling, Chang-Guo Zhan Nov 2011

Removing Aluminum From Solution Using Chelating Compounds And Immobilized Tethered Chelators, Robert A. Yokel, Wesley R. Harris, Christopher D. Spilling, Chang-Guo Zhan

Pharmaceutical Sciences Faculty Patents

Methods are described for removing aluminum from a solution using novel di- and tripodal compounds as chelators.


A Brief Overview Of Adolescent Developmental Problems In Hong Kong, Daniel T. L. Shek, Hing Keung Ma, Rachel C. F. Sun Nov 2011

A Brief Overview Of Adolescent Developmental Problems In Hong Kong, Daniel T. L. Shek, Hing Keung Ma, Rachel C. F. Sun

Pediatrics Faculty Publications

Several adolescent developmental problems in Hong Kong are briefly reviewed in this paper. First, rising adolescent substance abuse trends are described. Second, Internet use problems and Internet addiction among young people are examined. Third, worrying trends in adolescent sexuality are identified. Fourth, phenomena on bullying among young people are reviewed. Finally, phenomena related to adolescent materialistic orientation are focused upon. With reference to these adolescent developmental problems, possible solutions are briefly discussed particularly with reference to the ecological perspective. It is argued that the related scientific literature provides useful pointers for designing the curriculum in the extension phase of the …


Development Of A New Curriculum In A Positive Youth Development Program: The Project P.A.T.H.S. In Hong Kong, Daniel T. L. Shek, Hing Keung Ma, Rachel C. F. Sun Nov 2011

Development Of A New Curriculum In A Positive Youth Development Program: The Project P.A.T.H.S. In Hong Kong, Daniel T. L. Shek, Hing Keung Ma, Rachel C. F. Sun

Pediatrics Faculty Publications

The design of a new curriculum in a positive youth development program (Project P.A.T.H.S.) in Hong Kong is outlined. The Tier 1 Program of the original phase of the Project P.A.T.H.S. is a universal positive youth development program for students in Secondary 1 to Secondary 3 with the curricula developed by a research team comprising scholars in different disciplines (e.g., social work, psychology, and education). The 120 teaching units are designed with reference to 15 positive youth development constructs identified in the successful positive youth development programs. In the extension phase of the project, a new curriculum with 60 teaching …


Open Access: Good For Readers, Authors, And Journals, James M. Donovan, Carol A. Watson Nov 2011

Open Access: Good For Readers, Authors, And Journals, James M. Donovan, Carol A. Watson

James M. Donovan

Readers, authors, and even law journal publishers will all achieve their different but related interests by adopting open access principles. Readers of every kind will have more efficient access to the materials they need to pursue their intellectual and informational goals; authors will see their works read and cited by a broader audience; and law reviews and journals can raise their own profiles without injuring their revenue streams from fee-based sources. Open access works for everyone, and is the future of information creation and distribution.


The Science Of Public Health Delivery: Evidence, Uncertainties & Research Needs, Glen P. Mays Nov 2011

The Science Of Public Health Delivery: Evidence, Uncertainties & Research Needs, Glen P. Mays

Health Management and Policy Presentations

Policy initiatives to reform the nation's health system increasingly recognize the need to incorporate public health and prevention strategies. The nation's delivery system for public health, however, varies widely across states and communities in its structure, authority, and capabilities. This session examines research from the growing field of public health services and systems research to identify directions for improving public health delivery.


Open Access: Good For Readers, Authors, And Journals, James M. Donovan, Carol A. Watson Nov 2011

Open Access: Good For Readers, Authors, And Journals, James M. Donovan, Carol A. Watson

Law Faculty Scholarly Articles

Readers, authors, and even law journal publishers will all achieve their different but related interests by adopting open access principles. Readers of every kind will have more efficient access to the materials they need to pursue their intellectual and informational goals; authors will see their works read and cited by a broader audience; and law reviews and journals can raise their own profiles without injuring their revenue streams from fee-based sources. Open access works for everyone, and is the future of information creation and distribution.


Pay No Attention To That Repository Behind The Curtain: Focusing On Services, Sarah L. Shreeves Nov 2011

Pay No Attention To That Repository Behind The Curtain: Focusing On Services, Sarah L. Shreeves

Key to Unlocking Scholarship: Institutional Repositories

Over the last 10 years, digital repositories of all sorts have become a common feature in research libraries and consortia. Such repositories allow libraries to collect, manage, preserve, and provide access to an enormous range of content: institutional research and scholarship, university and library electronic records, digitized and born-digital archival and special collections, and digitized and born-digital books and journals. For the most part, the repository itself—the infrastructure where libraries put this content—has been the focus of attention. More recently, however, the repository itself has begun to shift to the background, to truly serve as infrastructure, while the services that …


Estimating The Value Of Public Health Services & Systems: Evidence, Uncertainties, And Research Needs, Glen P. Mays Nov 2011

Estimating The Value Of Public Health Services & Systems: Evidence, Uncertainties, And Research Needs, Glen P. Mays

Health Management and Policy Presentations

The Affordable Care Act authorized the largest expansion in federal funding for public health services and delivery systems in decades. These provisions, designed to support programs and services that promote health and prevent disease and injury on a population-wide basis, remain controversial because of uncertainties regarding their effectiveness in improving health and constraining medical cost growth. This session examines a series of recent studies to shed light on the health and economic value of spending on public health.


Fungal Desaturases And Related Methods, David F. Hildebrand, Suryadevara S. Rao, John Thoguru Nov 2011

Fungal Desaturases And Related Methods, David F. Hildebrand, Suryadevara S. Rao, John Thoguru

Plant and Soil Sciences Faculty Patents

The presently-disclosed subject matter provides isolated nucleic acid and amino acid sequences encoding mushroom desaturase polypeptides that are active with both palmitic and stearic acid, as well as vectors and transgenic plant cells comprising nucleic acids of the presently-disclosed subject matter. The presently-disclosed subject matter further provides methods of producing monounsaturated fatty acids, such as palmitoleic acid (16:1), and monounsaturated fatty acids prepared by the methods disclosed herein.


Nanoparticulate Formulations Of Mithramycin Analogs For Enhanced Cytotoxicity, Daniel Scott, Jürgen Rohr, Younsoo Bae Nov 2011

Nanoparticulate Formulations Of Mithramycin Analogs For Enhanced Cytotoxicity, Daniel Scott, Jürgen Rohr, Younsoo Bae

Pharmaceutical Sciences Faculty Publications

Mithramycin (MTM), a natural product of soil bacteria from the Streptomyces genus, displays potent anticancer activity but has been limited clinically by severe side effects and toxicities. Engineering of the MTM biosynthetic pathway has produced the 3-side-chain-modified analogs MTM SK (SK) and MTM SDK (SDK), which have exhibited increased anticancer activity and improved therapeutic index. However, these analogs still suffer from low bioavailability, short plasma retention time, and low tumor accumulation. In an effort to aid with these shortcomings, two nanoparticulate formulations, poly(ethylene glycol)-poly(aspartate hydrazide) self-assembled and cross-linked micelles, were investigated with regard to the ability to load and pH …


Age-Associated Disruption Of Molecular Clock Expression In Skeletal Muscle Of The Spontaneously Hypertensive Rat, Mitsunori Miyazaki, Elizabeth Schroder, Stephanie E. Edelmann, Michael E. Hughes, Karl Kornacker, C. William Balke, Karyn A. Esser Nov 2011

Age-Associated Disruption Of Molecular Clock Expression In Skeletal Muscle Of The Spontaneously Hypertensive Rat, Mitsunori Miyazaki, Elizabeth Schroder, Stephanie E. Edelmann, Michael E. Hughes, Karl Kornacker, C. William Balke, Karyn A. Esser

Physiology Faculty Publications

It is well known that spontaneously hypertensive rats (SHR) develop muscle pathologies with hypertension and heart failure, though the mechanism remains poorly understood. Woon et al. (2007) linked the circadian clock gene Bmal1 to hypertension and metabolic dysfunction in the SHR. Building on these findings, we compared the expression pattern of several core-clock genes in the gastrocnemius muscle of aged SHR (80 weeks; overt heart failure) compared to aged-matched control WKY strain. Heart failure was associated with marked effects on the expression of Bmal1, Clock and Rora in addition to several non-circadian genes important in regulating skeletal muscle phenotype including …