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Effect Of Muscle Length On Cross-Bridge Kinetics In Intact Cardiac Trabeculae At Body Temperature, Nima Milani-Nejad, Ying Xu, Jonathan P. Davis, Kenneth S. Campbell, Paul M. L. Janssen

Physiology Faculty Publications

Dynamic force generation in cardiac muscle, which determines cardiac pumping activity, depends on both the number of sarcomeric cross-bridges and on their cycling kinetics. The Frank–Starling mechanism dictates that cardiac force development increases with increasing cardiac muscle length (corresponding to increased ventricular volume). It is, however, unclear to what extent this increase in cardiac muscle length affects the rate of cross-bridge cycling. Previous studies using permeabilized cardiac preparations, sub-physiological temperatures, or both have obtained conflicting results. Here, we developed a protocol that allowed us to reliably and reproducibly measure the rate of tension redevelopment (k_tr; which depends …

Successfully Climbing The "Stairs": Surmounting Failed Translation Of Experimental Ischemic Stroke Treatments, Michael Kahle, Gregory J. Bix

Sanders-Brown Center on Aging Faculty Publications

The Stroke Therapy Academic Industry Roundtable (STAIR) provided initial (in 1999) and updated (in 2009) recommendations with the goal of improving preclinical stroke therapy assessment and to increase the translational potential of experimental stroke treatments. It is important for preclinical stroke researchers to frequently consider and revisit these concepts, especially since promising experimental stroke treatments continue to fail in human clinical trials. Therefore, this paper will focus on considerations for several key aspects of preclinical stroke studies including the selection and execution of the animal stroke model, drug/experimental treatment administration, and outcome measures to improve experimental validity and translation potential. …

Orofacial Neuropathic Pain Mouse Model Induced By Trigeminal Inflammatory Compression (Tic) Of The Infraorbital Nerve, Fei Ma, Liping Zhang, Danielle Lyons, Karin N. Westlund

Physiology Faculty Publications

BACKGROUND: Trigeminal neuropathic pain attacks can be excruciating for patients, even after being lightly touched. Although there are rodent trigeminal nerve research models to study orofacial pain, few models have been applied to studies in mice. A mouse trigeminal inflammatory compression (TIC) model is introduced here which successfully and reliably promotes vibrissal whisker pad hypersensitivity.

RESULTS: The chronic orofacial neuropathic pain model is induced after surgical placement of chromic gut suture in the infraorbital nerve fissure in the maxillary bone. Slight compression and chemical effects of the chromic gut suture on the portion of the infraorbital nerve contacted cause mild …

Testing Diagnostics Of Nuclear Activity And Star Formation In Galaxies At Z > 1, Jonathan R. Trump, Nicholas P. Konidaris, Guillermo Barro, David C. Koo, Dale D. Kocevski, Stéphanie Juneau, Benjamin J. Weiner, S. M. Faber, Ian S. Mclean, Renbin Yan, Pablo G. Pérez-González, Victor Villar

Physics and Astronomy Faculty Publications

We present some of the first science data with the new Keck/MOSFIRE instrument to test the effectiveness of different AGN/SF diagnostics at z ~ 1.5. MOSFIRE spectra were obtained in three H-band multi-slit masks in the GOODS-S field, resulting in 2 hr exposures of 36 emission-line galaxies. We compare X-ray data with the traditional emission-line ratio diagnostics and the alternative mass-excitation and color-excitation diagrams, combining new MOSFIRE infrared data with previous HST/WFC3 infrared spectra (from the 3D-HST survey) and multiwavelength photometry. We demonstrate that a high [O III]/Hβ ratio is insufficient as an active galactic nucleus (AGN) indicator …

The Central Molecular Gas Structure In Liners With Low-Luminosity Active Galactic Nuclei: Evidence For Gradual Disappearance Of The Torus, F. Müller-Sánchez, M. A. Prieto, M. Mezcua, R. I. Davies, M. A. Malkan, Moshe Elitzur

Physics and Astronomy Faculty Publications

We present observations of the molecular gas in the nuclear environment of three prototypical low-luminosity active galactic nuclei (LLAGNs), based on VLT/SINFONI AO-assisted integral-field spectroscopy of H₂ 1-0 S(1) emission at angular resolutions of ~0.''17. On scales of 50-150 pc, the spatial distribution and kinematics of the molecular gas are consistent with a rotating thin disk, where the ratio of rotation (V) to dispersion (σ) exceeds unity. However, in the central 50 pc, the observations reveal a geometrically and optically thick structure of molecular gas (V/σ < 1 and N _H > 10²³ cm^{–2 …}

Human Calmodulin Methyltransferase: Expression, Activity On Calmodulin, And Hsp90 Dependence, Sophia Magen, Roberta Magnani, Sitvanit Haziza, Eli Hershkovitz, Robert Houtz, Franca Cambi, Ruti Parvari

Horticulture Faculty Publications

Deletion of the first exon of calmodulin-lysine N-methyltransferase (CaM KMT, previously C2orf34) has been reported in two multigene deletion syndromes, but additional studies on the gene have not been reported. Here we show that in the cells from 2p21 deletion patients the loss of CaM KMT expression results in accumulation of hypomethylated calmodulin compared to normal controls, suggesting that CaM KMT is essential for calmodulin methylation and there are no compensatory mechanisms for CaM methylation in humans. We have further studied the expression of this gene at the transcript and protein levels. We have identified 2 additional …

Use Of The County Health Rankings By Local Health Departments In Florida, 2010 - 2011, Nancy L. Winterbauer, Bonita Sorensen, James B. Tidwell

Frontiers in Public Health Services and Systems Research

This paper describes how local health departments (LHDs) in Florida used the County Health Rankings over the first two years of their release (2010 – 2011). We surveyed LHD leadership to describe if, how and to what extent the Rankings were used by Florida’s 67 LHDs to improve the health of their communities and describe changes in use from the 2010 to the 2011 release. Our results indicate substantial use of the Rankings by Florida’s LHDs, particularly as applied to community health assessments, staff education, as a starting point for examining other indicators and databases, and in grant applications. From …

Effectiveness And Challenges For Implementing Quality Improvement Activities In Nebraska’S Local Health Departments, Li-Wu Chen, Anh Nguyen, Janelle J. Jacobson, Diptee Ojha, David Palm

Frontiers in Public Health Services and Systems Research

What is already known on this topic? Although the implementation strategies and effectiveness of quality improvement (QI) activities have been examined extensively for many industries, including the health care sector, very few studies have focused on QI activities in the public health context.

What is added by this report? The study results indicated that Nebraska’s LHDs still face significant barriers for QI implementation, including low capacity, knowledge gaps, inadequate resources, and low institutional QI maturity.

What are the implications for public health practice/policy/research? Policy makers and LHDs should provide QI training and external QI expertise to LHD staff and better …

Building Capacity To Support And Study Qi In Local Georgia Public Health Systems, William C. Livingood, Nandi Marshall, Angela Peden, Ketty Gonzales, Gulzar H. Shah, Russ Toal, Kellie Penix, Dayna Alexander, Kay Davis, Sylvester Nixon, Purity Cummings, William Riley, Lynn Woodhouse

Frontiers in Public Health Services and Systems Research

The study of quality improvement within Georgia’s local public health systems provides important insight into the use of regional bodies as quality improvement (QI) collaboratives and multijurisdictional entities. This report describes QI initiatives following a RWJF funded quick strike research grant to assess health district capacity to conduct QI in Georgia’s local public health systems. These QI initiatives use QI to improve public health outcomes including: Adolescent pregnancy and Sexually Transmitted Infection prevention, HIV prevention and control, and HIV Management.

Tax Levy Financing For Local Public Health: Relationships Between Fiscal Allocation, Fiscal Effort And Fiscal Capacity, William Riley, Kim J. Gearin, Carmen D. Parrotta, Jill Briggs, M. Elizabeth Gyllstrom

Frontiers in Public Health Services and Systems Research

This study examines property tax levy (local tax levy) as a source of local health department (LHD) funding during a five year period (2006-2010) in all Minnesota counties by assessing fiscal effort, fiscal allocation and fiscal capacity. Local health departments rely on pluralistic funding from local, state, federal and private sources. However, local tax levy funding is unexplored and little is known regarding the extent of fiscal allocation (tax levy used for LHD), fiscal effort (potential amount of tax levy available for LHD), and fiscal capacity (wealth of community). More important it is not known to what extent variation between …

Mandated Activities And Limited Decision-Making Authority Among Local Public Health Officials, Betty Bekemeier, Anthony L-T Chen, Nami Kawakyu

Frontiers in Public Health Services and Systems Research

Local public health department leaders face difficult decisions regarding the allocation of increasingly scarce resources, yet existing evidence for public health decision making, while still limited, is underutilized by public health officials. Participants in this study described processes regarding resource allocation in response to local budget cuts as based largely on legally mandated activities and categorical funding and perceived these factors as limiting much of their agency-level decision making to a relatively small portion of flexible funding. In the limited areas in which they perceived themselves to have flexibility, they generally considered their agencies to have very little capacity for …

Evidence-Based Decision Making In Local Health Departments, Linda Weiss, Collette Sosnowy, Christopher M. Maylahn, Nancy J. Katagiri, Sylvia Pirani

Frontiers in Public Health Services and Systems Research

Evidence-based decision making (EBDM) represents an important strategy to increase efficacy and efficiency of public health programs and practice. There is insufficient information on the application of EBDM among local health departments (LHDs). This qualitative study examined use of EBDM in New York State (NYS) LHDs and factors facilitating and impeding its adoption through interviews and focus groups with 47 LHD commissioners, health directors, and other upper-level staff. Findings suggest variability in application of EBDM in NYS LHDs. A number of internal factors (e.g., staff capacity, organizational culture) and external factors (e.g., policy environment, appropriate and …

From The Frontier: Translating Research To Practice, Paul C. Erwin

Frontiers in Public Health Services and Systems Research

The purpose of this invited article is to describe the process of translating research into public health practice. An example is provided, showing how questions arose in the practice setting, a researcher was identified to help answer the questions, and findings from the research were applied in the practice setting. In this example, Dr. Lea LaFave (Community Health Institute/JSI in New Hampshire) worked with Dr. Danielle Varda (Assistant Professor at the University of Colorado/ Denver, School of Public Affairs) to use social network analysis to better understand a network of coalitions focused on underage substance abuse. The social network analysis …

Stimulating Public Health Improvement In Complex And Constrained Delivery Systems: Findings From The Public Health Pbrns, Glen P. Mays

Frontiers in Public Health Services and Systems Research

The Robert Wood Johnson Foundation’s Public Health Practice-Based Research Networks Program sponsored a series of studies to examine how public health decision-makers are responding to accreditation, quality improvement, and public reporting initiatives amid the ongoing fiscal pressures. Overall, the evidence to date indicates that these initiatives represent promising strategies for strengthening evidence-based decision-making and expanding the delivery of evidence-tested programs and policies in local public health settings. Continued, comparative research and evaluation activities are needed to provide more definitive evidence about which combination of strategies work best, for which population groups, in which community and organizational settings, and why.

Multiple Regulatory Mechanisms Control B-1 B Cell Activation, Vishal Sindhava, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

B-1 cells constitute a unique subset of B cells identified in several species including mice and humans. B-1 cells are further subdivided into B-1a and B-1b subsets as the former but not the later express CD5.The B-1a subset contributes to innate type of immune responses while the B-1b B cell subset contributes to adaptive responses. B-1 cell responses to B cell receptor (BCR) as well as Toll-like receptor (TLR) ligation are tightly regulated due to the cross-reactivity of antigen specific receptors on B-1 cells to self-antigens. B-1 cells are elevated in several autoimmune diseases. CD5 plays a major role in …

Global Profiling Of Alternative Splicing Events And Gene Expression Regulated By Hnrnph/F, Erming Wang, Vahid Aslanzadeh, Filomena Papa, Haiyan Zhu, Pierre De La Grange, Franca Cambi

Neurology Faculty Publications

In this study, we have investigated the global impact of heterogeneous nuclear Ribonuclear Protein (hnRNP) H/F-mediated regulation of splicing events and gene expression in oligodendrocytes. We have performed a genome-wide transcriptomic analysis at the gene and exon levels in Oli-neu cells treated with siRNA that targets hnRNPH/F compared to untreated cells using Affymetrix Exon Array. Gene expression levels and regulated exons were identified with the GenoSplice EASANA algorithm. Bioinformatics analyses were performed to determine the structural properties of G tracts that correlate with the function of hnRNPH/F as enhancers vs. repressors of exon inclusion. Different types of alternatively spliced events …

Elevated Cardiovascular Risk Among Adults With Obstructive And Restrictive Airway Functioning In The United States: A Cross-Sectional Study Of The National Health And Nutrition Examination Survey From 2007 - 2010, Earl S. Ford, Ann G. Wheaton, David M. Mannino, Latitia Presley-Cantrell, Chaoyang Li, Janet B. Croft

David M. Mannino

Background

Reasons for the excess risk for cardiovascular disease among people with chronic obstructive pulmonary disease remain unclear. Our objective was to examine the cardiovascular risk profile for adults with obstructive and restrictive impairments of lung functioning in a representative sample of adults from the United States.

Methods

We used data from adults aged 20–79 years who participated in the National Health and Nutrition Examination Survey from 2007 to 2010 and had a pulmonary function test. The severity of obstructive impairment was defined by adapting the Global Initiative for Chronic Obstructive Lung Disease criteria.

Results

Among 7249 participants, 80.9% had …

Elevated Cardiovascular Risk Among Adults With Obstructive And Restrictive Airway Functioning In The United States: A Cross-Sectional Study Of The National Health And Nutrition Examination Survey From 2007-2010, Earl S. Ford, Anne G. Wheaton, David M. Mannino, Letitia Presley-Cantrell, Chaoyang Li, Janet B. Croft

Preventive Medicine and Environmental Health Faculty Publications

BACKGROUND: Reasons for the excess risk for cardiovascular disease among people with chronic obstructive pulmonary disease remain unclear. Our objective was to examine the cardiovascular risk profile for adults with obstructive and restrictive impairments of lung functioning in a representative sample of adults from the United States.

METHODS: We used data from adults aged 20-79 years who participated in the National Health and Nutrition Examination Survey from 2007 to 2010 and had a pulmonary function test. The severity of obstructive impairment was defined by adapting the Global Initiative for Chronic Obstructive Lung Disease criteria.

RESULTS: Among 7249 participants, 80.9% had …

Treatment Of Klebsiella Pneumoniae Carbapenemase (Kpc) Infections: A Review Of Published Case Series And Case Reports, Grace C. Lee, David S. Burgess

Pharmacy Practice and Science Faculty Publications

The emergence of Klebsiella pneumoniae carbapenemases (KPCs) producing bacteria has become a significant global public health challenge while the optimal treatment remains undefined. We performed a systematic review of published studies and reports of treatment outcomes of KPC infections using MEDLINE (2001-2011). Articles or cases were excluded if one of the following was fulfilled: no individual patient data provided, no treatment regimen specified, no treatment outcome specified, report of colonization, or greater than three antibiotics were used to treat the KPC infection. Data extracted included patient demographics, site of infection, organism, KPC subtype, antimicrobial therapy directed at KPC-infection, and treatment …

Effects Of Exercise On Ampk Signaling And Downstream Components To Pi3k In Rat With Type 2 Diabetes, Shicheng Cao, Bowen Li, Xuejie Yi, Bo Chang, Beibei Zhu, Zhenzhen Lian, Zhaoran Zhang, Gang Zhao, Huili Liu, He Zhang

Barnstable Brown Diabetes Center Faculty Publications

Exercise can increase skeletal muscle sensitivity to insulin, improve insulin resistance and regulate glucose homeostasis in rat models of type 2 diabetes. However, the potential mechanism remains poorly understood. In this study, we established a male Sprague-Dawley rat model of type 2 diabetes, with insulin resistance and β cell dysfunction, which was induced by a high-fat diet and low-dose streptozotocin to replicate the pathogenesis and metabolic characteristics of type 2 diabetes in humans. We also investigated the possible mechanism by which chronic and acute exercise improves metabolism, and the phosphorylation and expression of components of AMP-activated protein kinase (AMPK) and …

Export Strength And Opportunities For Kentucky Industries, Christopher R. Bollinger, Derrick Jenniges

CBER Research Report

Executive Summary:

This project's primary goal is to quantify export strengths and opportunities in Kentucky industries. We measure export strength as the relative dollar value of exports per worker in four digit industries using U.S. dollar value of exports per worker as the base. Tables were prepared for total exports and a selection of 50 countries representing 98.5% of Kentucky exports and 93.2% of U.S. exports. In addition to the export index, a measure of industry strength based upon labor and comparisons to regional competitor states is provided.

• Industries with a low index value, either overall or for specific countries, …

Luteolin Inhibits Human Prostate Tumor Growth By Suppressing Vascular Endothelial Growth Factor Receptor 2-Mediated Angiogenesis, Poyil Pratheeshkumar, Young-Ok Son, Amit Budhraja, Xin Wang, Songze Ding, Lei Wang, Andrew Hitron, Jeong-Chae Lee, Donghern Kim, Sasidharan Padmaja Divya, Gang Chen, Zhuo Zhang, Jia Luo, Xianglin Shi

Toxicology and Cancer Biology Faculty Publications

Angiogenesis, the formation of new blood vessels from pre-existing vascular beds, is essential for tumor growth, invasion, and metastasis. Luteolin is a common dietary flavonoid found in fruits and vegetables. We studied the antiangiogenic activity of luteolin using in vitro, ex vivo, and in vivo models. In vitro studies using rat aortic ring assay showed that luteolin at non-toxic concentrations significantly inhibited microvessel sprouting and proliferation, migration, invasion and tube formation of endothelial cells, which are key events in the process of angiogenesis. Luteolin also inhibited ex vivo angiogenesis as revealed by chicken egg chorioallantoic membrane assay (CAM) …

Doublesex Target Genes In The Red Flour Beetle, Tribolium Castaneum, Jayendra Nath Shukla, Subba Reddy Palli

Entomology Faculty Publications

Sex determination cascade in insects terminates with the production of sex-specific protein, Doublesex (Dsx). We identified the dsx homolog (Tcdsx) in Tribolium castaneum. The pre-mRNA of Tcdsx is sex-specifically spliced into three female (Tcdsxf1, Tcdsxf2 and Tcdsxf3) and one male-specific (Tcdsxm) isoforms. Cis-regulatory elements potentially involved in sex-specific splicing of the Tcdsx pre-mRNA were identified in the female-specific exon and the adjoining intronic sequences. All the three female-specific TcDsx proteins share common OD1 and OD2 domains and differ in their C-terminal sequences. Knockdown of Tcdsx resulted in a reduction in the oocyte development, egg production and hatching of eggs laid. …

Public Health Return On Investment: Making The Case, Glen P. Mays

Health Management and Policy Presentations

Fiscal pressures and policy imperatives have created a need for rigorous economic analyses of public health programs and policies. ROI analyses can reveal whether the benefits of public health strategies justify their costs, who realizes these benefits and costs, and under what circumstances.

Comparative Effectiveness Research And Patient Centered Outcomes Research In Public Health Settings: Design, Analysis, And Funding Considerations, Glen P. Mays

Health Management and Policy Presentations

The principles and methods of CER and PCOR have developed primarily with therapeutics in mind, but they must also be applied to the study of public health programs, policies, and delivery systems. This session surveys the emerging field, and provides examples of CER/PCOR methods applied in public health settings using practice-based research networks (PBRNs).

Depletion Of Endothelial Or Smooth Muscle Cell-Specific Angiotensin Ii Type 1a Receptors Does Not Influence Aortic Aneurysms Or Atherosclerosis In Ldl Receptor Deficient Mice, Debra L. Rateri, Jessica J. Moorleghen, Victoria Knight, Anju Balakrishnan, Deborah A. Howatt, Lisa A. Cassis, Alan Daugherty

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Whole body genetic deletion of AT1a receptors in mice uniformly reduces hypercholesterolemia and angiotensin II-(AngII) induced atherosclerosis and abdominal aortic aneurysms (AAAs). However, the role of AT1a receptor stimulation of principal cell types resident in the arterial wall remains undefined. Therefore, the aim of this study was to determine whether deletion of AT1a receptors in either endothelial cells or smooth muscle cells influences the development of atherosclerosis and AAAs.

METHODOLOGY/PRINCIPAL FINDINGS: AT1a receptor floxed mice were developed in an LDL receptor -/- background. To generate endothelial or smooth muscle cell specific deficiency, AT1a receptor floxed mice were bred with …

Reactive Oxygen Species Production And Brugia Pahangi Survivorship In Aedes Polynesiensis With Artificial Wolbachia Infection Types, Elizabeth S. Andrews, Philip R. Crain, Yuqing Fu, Daniel K. Howe, Stephen L. Dobson

Entomology Faculty Publications

Heterologous transinfection with the endosymbiotic bacterium Wolbachia has been shown previously to induce pathogen interference phenotypes in mosquito hosts. Here we examine an artificially infected strain of Aedes polynesiensis, the primary vector of Wuchereria bancrofti, which is the causative agent of Lymphatic filariasis (LF) throughout much of the South Pacific. Embryonic microinjection was used to transfer the wAlbB infection from Aedes albopictus into an aposymbiotic strain of Ae. polynesiensis. The resulting strain (designated "MTB") experiences a stable artificial infection with high maternal inheritance. Reciprocal crosses of MTB with naturally infected wild-type Ae. polynesiensis demonstrate strong bidirectional incompatibility. Levels of reactive …

A Hunter Virus That Targets Both Infected Cells And Hiv Free Virions: Implications For Therapy, Cody Greer, Gisela García-Ramos

Biology Faculty Publications

The design of 'hunter' viruses aimed at destroying human immunodeficiency virus (HIV) infected cells is an active area of research that has produced promising results in vitro. Hunters are designed to target exposed viral envelope proteins in the membranes of infected cells, but there is evidence that the hunter may also target envelope proteins of free HIV, inducing virus-virus fusion. In order to predict the effects of this fusion on therapy outcomes and determine whether fusion ability is advantageous for hunter virus design, we have constructed a model to account for the possibility of hunter-HIV fusion. The study was based …

The P2y(12) Antagonists, 2mesamp And Cangrelor, Inhibit Platelet Activation Through P2y(12)/G(I)-Dependent Mechanism, Binggang Xiang, Guoying Zhang, Hongmei Ren, Manjula Sunkara, Andrew J. Morris, T. Kent Gartner, Susan S. Smyth, Zhenyu Li

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: ADP is an important physiological agonist that induces integrin activation and platelet aggregation through its receptors P2Y(1) (Gα(q)-coupled) and P2Y(12) (Gα(i)-coupled). P2Y(12) plays a critical role in platelet activation and thrombosis. Adenosine-based P2Y(12) antagonists, 2-methylthioadenosine 5'-monophosphate triethylammonium salt hydrate (2MeSAMP) and Cangrelor (AR-C69931MX) have been widely used to demonstrate the role of P2Y(12) in platelet function. Cangrelor is being evaluated in clinical trials of thrombotic diseases. However, a recent study reported that both 2MeSAMP and Cangrelor raise intra-platelet cAMP levels and inhibit platelet aggregation through a P2Y(12)-independent mechanism.

METHODOLOGY/PRINCIPAL FINDINGS: The present work, using P2Y(12) deficient mice, sought to …

Process And Domain Specificity In Regions Engaged For Face Processing: An Fmri Study Of Perceptual Differentiation, Heather R. Collins, Xun Zhu, Ramesh S. Bhatt, Jonathan D. Clark, Jane E. Joseph

Psychology Faculty Publications

The degree to which face-specific brain regions are specialized for different kinds of perceptual processing is debated. This study parametrically varied demands on featural, first-order configural, or second-order configural processing of faces and houses in a perceptual matching task to determine the extent to which the process of perceptual differentiation was selective for faces regardless of processing type (domain-specific account), specialized for specific types of perceptual processing regardless of category (process-specific account), engaged in category-optimized processing (i.e., configural face processing or featural house processing), or reflected generalized perceptual differentiation (i.e., differentiation that crosses category and processing type boundaries). ROIs were …